Objective To explore the wearing status and actual noise reduction effect of hearing protectors among noise workers in a typical automobile manufacturing enterprise. Methods In April 2024, an occupational hazard factor testing was carried out in an automobile manufacturing industry, and at the same time, the hearing protection fit test was conducted for noise workers. Intervention and guidance were provided to those who did not pass the minimum standard of baseline PAR. The difference in PAR between baseline and post-intervention was compared, and the effectiveness of hearing protector wearing method training was evaluated. Results The exceeding rate of the company's noise operation post was 50.77% (66/130). The baseline PAR of the subjects with working experience of less than 15 years and wearing hearing protectors throughout noisy work was higher, and the differences were statistically significant (P<0.05). Compared with those with 80dB≤L_{EX, 8h}<85dB, more research subjects with L_{EX, 8h}≥85dB failed baseline PAR (39.13%). After intervention, the PAR of the subjects who did not pass the minimum standard of baseline PRA increased from 2.0 (0.0, 5.3) to 17.0 (14.8, 20.0), and the protection level was significantly improved, and the difference was statistically significant (P<0.01). Conclusion The individual fit test of hearing protector is an important means to evaluate the actual noise reduction level of hearing protector and guide the selection of hearing protection models. Corporate training can help improve the PAR of hearing protectors.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective To establish an "human serum - porcine aortic endothelial cells (PAEC) - human platelets" in vitro model and explore the mechanism of xenotransplantation-related coagulation dysfunction mediated by immune complexes - platelet FcγRⅡa (CD32a) receptor. Methods Healthy human serum was co-incubated with PAEC to prepare the supernatant containing immune complexes, which was then used to stimulate healthy human platelets, or directly treated with the serum of xenogeneic liver transplant recipients. Flow cytometry was used to detect platelet activation markers CD62P and surface IgG binding levels, and the platelet adhesion function was evaluated by platelet-PAEC adhesion experiments. CD32a blocking antibody IV.3 and SYK blocker SKYIN 4 were used to clarify the signaling pathways. Results The supernatant from the co-incubation of healthy human serum and PAEC could significantly induce platelet activation and endothelial adhesion. The use of the serum from xenogeneic liver transplant recipients could also significantly induce platelet activation. Antibody IV.3 and SYK blocker SKYIN 4 could significantly inhibit these effects. Conclusions In xenotransplantation, the immune complexes formed by human serum antibodies and porcine endothelial antigens may induce abnormal platelet activation through the platelet CD32a receptor, which is an important mechanism of non-complement-dependent post-transplant coagulation dysfunction, providing a new target for the intervention of coagulation complications in xenotransplantation.

ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

Objective To explore the clinical efficacy of robot-assisted coronary artery bypass grafting through a small incision in the left intercostal space in the treatment of multivessel coronary disease. Methods A retrospective analysis was conducted on the clinical data of patients who underwent coronary artery bypass grafting through a small incision in the left intercostal space at Central China Fuwai Hospital of Zhengzhou University from January 1, 2023 to October 15, 2024. Patients were divided into a robotic group and a minimally invasive group based on whether the surgery was assisted by the Da Vinci robot. Results A total of 81 patients were included, with 57 in the minimally invasive group, including 41 males and 16 females, with a median age of 65.0 (57.5, 69.5) years; and 24 in the robotic group, including 17 males and 7 females, with a median age of 61.0 (56.0, 69.0) years. There was no statistically significant difference in baseline data between the two groups (P>0.05). The robotic group had less intraoperative bleeding [300 (200, 438) mL vs. 500 (375, 600) mL, P=0.006], shorter postoperative mechanical ventilation time [15.0 (13.3, 23.5) h vs. 22.0 (15.5, 39.5) h, P=0.037], and lower incidence of postoperative pain [8 (33.3%) vs. 33 (57.9%), P=0.043]. The hospitalization cost in the robotic group was higher than that in the minimally invasive group [130491 (123298, 135691) yuan vs. 123892 (115543, 133449) yuan, P=0.023]. There was no statistical difference in postoperative laboratory indicators between the two groups (P>0.05). There was also no statistical difference in the duration of surgery, postoperative 24 h drainage volume, ICU stay time, postoperative hospital stay or incidences of perioperative compications including pleural effusion, transfusion, new-onset atrial fibrillation, acute kidney injury, non-union of incision, major cardiovascular and cerebrovascular adverse events, and reoperation between the two groups (P>0.05). Conclusion Compared with the minimally invasive group, the robotic group shows satisfactory efficacy and can effectively reduce postoperative pain and intraoperative bleeding, and shorten postoperative mechanical ventilation time.

Objective Exploring genetic differences among geographic strains of Anopheles sinensis in China. Methods Based on the mitochondrial cytochrome oxidase subunit I(COⅠ )and ribosomal the second internal transcribed spacer(ITS2), genetic distance analyses were conducted on An. sinensis samples collected nationwide. Results Genetic differentiation was observed within An. sinensis geographic strains, primarily reflected in the genetic distances of COⅠ sequences, with some distances between samples exceeding those between closely related species. However, ITS2 sequences showed relatively low levels of differentiation within geographic strains. No significant separation was observed, and gene exchange exhibited a random pattern among geographic strains. Conclusions Significant differences in genetic distance were observed among An. sinensis samples, along with evidence of interspecific continuity among sibling species. For the identification of closely related species using wild-collected Anopheles mosquitoes samples, reliance solely on commonly used barcodes such as COⅠ and ITS2 may be insufficient. Additional molecular markers, including COⅡ and D3 gene fragments, should also be considered. Caution should be exercised when using COⅠ genes to identify cryptic species, especially within Anopheles mosquitoes.

Objective To analyze the increase in hearing thresholds in different frequency bands of workers exposed to different characteristic noises and the influencing factors of binaural high-frequency hearing loss, and to provide theoretical support for occupational health monitoring in enterprises. Methods In 2021, noise-exposed workers were selected from typical noise-exposing enterprises as research subjects, and their occupational health examination data were tracked for three consecutive years. According to the on-site detection from 2021 to 2023, the cumulative noise exposure (CNE) was calculated. The chi-square test was used to compare the increase of the hearing threshold of workers exposed to different characteristic noises in different frequency bands. A generalized estimation equation was constructed to explore the influencing factors of high-frequency hearing loss in the research subjects. Results The age of the study subjects was 23-54 years old, with 1.6-20.1 years of working experience, mainly distributed in manufacturing workshops, technical workshops and public works workshops. The median LAeq,8h was 85.90 (84.5, 86.1) dB(A), and the average CNE was 94.3±2.6 dB(A). The number of people with increased hearing thresholds in each frequency band was 0.5kHz>6kHz>4kHz>3kHz>1kHz>2kHz. There were statistically significant differences in the increase of hearing thresholds in each frequency band, binaural speech frequency impairment, and high-frequency hearing loss among subjects with different characteristics (P<0.05). The detection rate of binaural speech frequency hearing loss was the highest in subjects aged>45 years, with a length of service of>15 years, and with a CNE>96dB(A). The detection rate of binaural high-frequency hearing loss was the highest in subjects aged 35-40 years, with a length of service of 5-10 years, and with a CNE>96dB(A).In addition, the detection rate of binaural speech frequency and high-frequency hearing loss increased with the increase of CNE(P<0.05). The GEE model showed that age>40 years and CNE>96dB(A) were risk factors for high-frequency hearing loss in both ears. Conclusion With increasing age and CNE, hearing thresholds rise across all frequency bands, elevating the risk of binaural speech-frequency and high-frequency hearing loss, thereby increasing the likelihood of occupational noise-induced deafness.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

OBJECTIVE: To investigate the anti-inflammatory effect of rutaecarpine (RUT) on monosodium urate crystal (MSU)-induced murine peritonitis in mice and further explored the underlying mechanism of RUT in lipopolysaccharide (LPS)/MSU-induced gout model in vitro. METHODS: In MSU-induced mice, 36 male C57BL/6 mice were randomly divided into 6 groups of 8 mice each group, including the control group, model group, RUT low-, medium-, and high-doses groups, and prednisone acetate group. The mice in each group were orally administered the corresponding drugs or vehicle once a day for 7 consecutive days. The gout inflammation model was established by intraperitoneal injection of MSU to evaluate the anti-gout inflammatory effects of RUT. Then the proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and the proportions of infiltrating neutrophils cytokines were detected by flow cytometry. In LPS/MSU-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and proinflammatory cytokines were measured by ELISA. The percentage of pyroptotic cells were detected by flow cytometry. Respectively, the mRNA and protein levels were measured by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, the nuclear translocation of nuclear factor κB (NF-κB) p65 was observed by laser confocal imaging. Additionally, surface plasmon resonance (SPR) and molecular docking were applied to validate the binding ability of RUT components to tumor necrosis factor α (TNF-α) targets. RESULTS: RUT reduced the levels of infiltrating neutrophils and monocytes and decreased the levels of the proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 6 (IL-6, all P<0.01). In vitro, RUT reduced the production of IL-1β, IL-6 and TNF-α. In addition, RT-PCR revealed the inhibitory effects of RUT on the mRNA levels of IL-1β, IL-6, cyclooxygenase-2 and TNF-α (P<0.05 or P<0.01). Mechanistically, RUT markedly reduced protein expressions of tumor necrosis factor receptor (TNFR), phospho-mitogen-activated protein kinase (p-MAPK), phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, phospho-NF-κB, phospho-kinase α/β, NOD-like receptor thermal protein domain associated protein 3 (NLRPS), cleaved-cysteinyl aspartate specific proteinase-1 and cleaved-gasdermin D in macrophages (P<0.05 or P<0.01). Molecularly, SPR revealed that RUT bound to TNF-α with a calculated equilibrium dissociation constant of 31.7 µmol/L. Molecular docking further confirmed that RUT could interact directly with the TNF-α protein via hydrogen bonding, van der Waals interactions, and carbon-hydrogen bonding. CONCLUSION RUT alleviated MSU-induced peritonitis and inhibited the TNFR1-MAPK/NF-κB and NLRP3 inflammasome signaling pathway to attenuate gouty inflammation induced by LPS/MSU in THP-1 macrophages, suggesting that RUT could be a potential therapeutic candidate for gout.
Animals ; NF-kappa B/metabolism* ; Male ; Indole Alkaloids/therapeutic use* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Inflammation/complications* ; Uric Acid ; Quinazolines/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Gout/chemically induced* ; Inflammasomes/metabolism* ; Cytokines/metabolism* ; THP-1 Cells ; Mitogen-Activated Protein Kinases/metabolism* ; Mice ; Molecular Docking Simulation ; Lipopolysaccharides ; Quinazolinones