In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Angle class Ⅱ malocclusion is often characterized by mandibular retraction and lip incompetence,which affects the patient's lateral appearance and may even lead to upper airway stenosis.It can be classified into dental and skeletal types.For skeletal class Ⅱ malocclusion patients with mandibular retraction during the peak growth period,mandibular anterior guidance with a functional orthodontic appliance is generally considered as the optimal clinical treatment approach.At present,there remains a paucity of clinical reports on the clinical application of bracket-free clear aligners in mandibular anterior guidance,both domestically and internationally.This article presented a case of an adolescent patient with skeletal class Ⅱ malocclusion accompanied with deep overbite treated with bracket-free clear aligner for mandibular anterior guidance in combination with intermaxillary class Ⅱ traction.During the treatment,vertical correction involved anterior intrusion of the anterior teeth to improve the deep overbite,while horizontal correction included maxillary and mandibular expansion to coordinate the width of the dental arches,and asymmetric anterior guidance was used to correct the midline deviation.After 35 months of treatment,the patient's convex facial profile and mandibular retrusion were significantly improved.The subspinale-nasion-supramentale angle(ANB)was decreased from 6.8° to 3.9°,the overbite and overjet were normalized,and the bilateral canine and molar reached a neutral relationship.The mentolabial sulcus depth(Si-LiPg′)and the soft tissue thickness of pogonion to pogonion(Pm-Pm′)were decreased,resulting in a shallower mentolabial sulcus and a more harmonized lateral facial soft tissue profile.The mandibular incisor to mandibular plane angle(IMPA)was decreased from 116.6° to 110.7°,indicating retraction of the lower incisors during mandibular anterior guidance.In conclusion,the orthodontic strategy of mandibular advancement with clear aligners in skeletal class Ⅱ malocclusion patients can avoid excessive overcompensation of the upper and lower anterior teeth and shorten the orthodontic treatment cycle.

Objective:To develop fluorescent nanoprobes with aggregation-induced emission characteristics and to systematically evaluate their optical properties, biosafety, anti-tumor activity, and imaging capability, thereby assessing their potential for early precision diagnosis and treatment of oral cancer in mice.Methods:Control probes (PEG@TPD) were prepared by encapsulating ( E)-4-(2-(4′-(1-phenyl-2,2-bis(4-methoxyphenyl)vinyl)biphenyl-4-yl)vinyl)-4-(dicyanomethylene)-4 H-chromene (TPD) using 1,2-distearoyl- SN-glycerol-3-phosphoethanolamine- N-polyethylene glycol 2000-maleimide as the carrier. Fluorescent nanoprobes (GE11-PEG@TPD) were subsequently fabricated by surface modification with the targeting GE11 peptide. The morphology and particle size of the nanoprobes were characterized by transmission electron microscopy and dynamic light scattering. The optical properties of the nanoprobes were analyzed using ultraviolet-visible spectrophotometry and fluorescence spectrophotometry. Mouse squamous carcinoma SCC-7 cells were randomly divided into six groups by the random number table method. The PBS, PEG@TPD, and GE11-PEG@TPD groups were not treated with light, while the PBS+L, PEG@TPD+L, and GE11-PEG@TPD+L groups were exposed to white light (25 W/cm 2, 10 min) at a nanoprobe concentration of 20 μg/ml (based on TPD concentration). Cell survival rate was assessed by the cell counting kit-8 assay. Cellular uptake, intracellular reactive oxygen species levels, and cytotoxicity were evaluated using laser scanning confocal microscopy. The apoptosis rate was evaluated by cell apoptosis assay. Twelve 6-week-old female C3H/HeN mice were randomly divided into two groups: PEG@TPD-1 group and GE11-PEG@TPD-1 group, with 6 mice in each group. Subcutaneous oral cancer models were established by injecting SCC-7 cell suspensions into the dorsal region of mice in two groups. Each mouse was intravenously administered 200 μl of PEG@TPD or GE11-PEG@TPD solution (1 mg/ml, based on TPD concentration). Tumor boundaries and scope were visualized using a small animal in vivo imaging system. At the optimal imaging time point, three mice from each group were euthanized, and major organs and tumor tissues were collected to measure probe accumulation. Statistical comparisons between two groups were performed using independent samples t-tests, while one-way or two-way analysis of variance was applied for multiple group comparisons. Results:Both PEG@TPD and GE11-PEG@TPD exhibited a relatively regular sphere, with average particle sizes of (92.76±8.80 and 117.50±6.40) nm, respectively. PEG@TPD showed two obvious absorption peaks at 352 and 444 nm. GE11 peptide showed a polypeptide characteristic absorption peak at 280 nm, GE11-PEG@TPD showed three characteristic absorption peaks at 280, 352 and 444 nm. Under dark conditions, cell survival rate remained above 80% even at a concentration of 160 μg/ml. After light irradiation, cell survival rate in the PEG@TPD+L group at 20 and 40 μg/ml [(68.2±5.2)% and (48.6±7.1)%] were higher than those in the GE11-PEG@TPD+L group [(55.0±2.8)% and (30.0±9.2)%], with statistically significant differences ( P<0.05, 0.01). At incubation time points of 2, 4, and 6 h, the relative fluorescence intensity of the GE11-PEG@TPD group (119.4±10.2, 192.9±14.2, and 234.1±4.8) were higher than those of the PEG@TPD group (98.6±7.5, 163.8±3.1, 204.6±11.2), with statistically significant differences (all P<0.05). The relative fluorescence intensity of the PEG@TPD+L and GE11-PEG@TPD+L group (68.5±4.7 and 86.8±10.0) were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups (6.1±8.0, 7.6±1.8, 4.7±4.2 and 21.1±7.6), with statistically significant differences (all P<0.01). And the difference between the GE11-PEG@TPD+L and PEG@TPD+L groups was also statistically significant ( P<0.05). Viable cell proportions in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups all exceeded 95.0%, while those in the PEG@TPD+L and GE11-PEG@TPD+L groups decreased to (11.1±3.7)% and (4.3±1.1)%, respectively, with a statistically significant difference between them ( P<0.05). The apoptotic cell proportions in the PEG@TPD+L and GE11-PEG@TPD+L groups [(40.5±4.3)% and (55.3±7.4)%] were higher than those in the PBS, PEG@TPD, GE11-PEG@TPD, and PBS+L groups [(27.3±2.0)%, (28.2±1.9)%, (28.6±1.2)%, and (29.7±3.0)%], with statistically significant differences ( P<0.05, 0.01). Moreover, the difference between the GE11-PEG@TPD+L and the PEG@TPD+L groups was also statistically significant ( P<0.01). The mean fluorescence intensities of the GE11-PEG@TPD-1 group at 1, 3, 5, 8, and 24 h, as well as in ex vivo tumor tissues[(5.2±0.8, 5.9±0.7, 6.6±1.0, 7.9±0.6, 7.8±0.7 and 20.6±3.5)×10 6 p/s/cm 2/sr] were all higher than those in the PEG@TPD-1 group [(3.2±0.7, 4.2±0.7, 4.6±0.9, 5.1±0.9, 4.7±0.9 and 14.2±1.8)×10 6 p/s/cm 2/sr], with statistically significant differences ( P<0.05, 0.01). Conclusions:The fluorescent nanoprobes exhibit uniform particle size, high photostability, and good biocompatibility. They demonstrate significant tumor-killing effects at the cellular level and possess tumor-targeting capability in vivo, showing promising application potential for the early precision diagnosis and treatment of oral cancer.

Objective In this study,the gas exchange performance and impact patterns of microalgae culture based on hollow fiber membrane technology were investigated for the culture of space microalgae.Methods The effects of parameters and conditions such as gas flow rate,membrane area and liquid flow rate on the CO2 fixation efficiency and fixation rate of hollow fiber membrane modules were studied,and the gas exchange performance of different parameters were compared by fitting formula.Results The gas flow rate and membrane area have a significant effect on the gas exchange performance of the module.With the increase of gas flow rate,the fixation rate of CO2 increases at first and then stabilizes,and the fixation efficiency of CO2 shows a continuous downward trend;with the increase of membrane area,the fixation rate and fixation efficiency of CO2 increase significantly,while the liquid flow rate has no significant effect on the gas exchange performance of the module.The highest CO2 fixation rate was 168.24 mg/(L·h)when the membrane area was 0.3m2 and the gas flow rate was 2.0 L/min.Conclusion The use of hollow fiber membrane technology can solve the problem of two-phase flow management in the gas exchange between algae culture and atmosphere,which has a better effect on gas exchange,and can provide reference for the design of gas exchange module of space microalgae photobioreactor.

Animals ; Callithrix ; Sex Factors ; Vocalization, Animal ; Sex Characteristics

Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.

Stromal interaction molecule 1 (STIM1) is a key component mediating store-operated calcium entry (SOCE), which controls the opening and closing of plasma membrane Ca 2+ channels by sensing the Ca 2+ content of endoplasmic reticulum luminal stores, and thus affects the processes of cell adhesion, migration, gene expression and proliferation. Studies have shown that STIM1 is abnormally expressed in a variety of cells such as neurons, endothelial cells and platelets during ischemic stroke (IS) development; it plays an important role in the pathological processes regulating hypertension, promoting thrombosis, activating cellular autophagy, mediating apoptosis and promoting neuroinflammation. This review summarizes the research progress of STIM1 in the development and prognostic assessment of IS, and seeks to provide theoretical references for potential therapeutic targets for IS.

Objective To investigate the efficacy of Jianpiwenyang Gel(SSWYG)for treating chronic diarrhea and explore its therapeutic mechanism.Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules(control group,n=40)or naval application with SSWYG(treatment group,n=40)for one week,after which symptoms of chronic diarrhea were evaluated.The Chinese medicine system pharmacology analysis platform(TCMSP),GeneCards,NCBI,OMIM database and GEO database(GSE14841)were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets.The key targets were obtained by topological analysis for Gene Ontology(GO)and KEGG analyses.The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software.Results In both groups,gastrointestinal symptom rating scale(GSRS),Bristol Scale and TCM syndrome scores significantly improved after the treatments(P<0.05),and better effects were observed in the treatment group(P<0.05).Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained,and 33 most probable ones were screened out by topological analysis.GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways.Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3,JNK,IL1B,IL6,and AKT1.JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG.Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN,suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.