The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Acute kidney injury (AKI) is a critical clinical condition characterized by rapid renal function decline, with high morbidity, mortality, and healthcare costs. Traditional Chinese medicine (TCM) has shown potential effects on mitigating oxidative stress and programmed cell death in AKI models. Scutellaria barbata D. Don (SB) and Scleromitrion diffusum (Willd.) R. J. Wang (SD), a classic TCM herbal pair exhibited anti-inflammatory and antioxidant activities. Using advanced chromatographic separation technology, we enriched the effective fractions of water extracts from SB-SD, obtaining self-assembled herbal nanoparticles (SB and SD nanoparticles, SSNPs) rich in flavonoids and terpenoids. These SSNPs demonstrated robust antioxidant properties in vitro and mitigated AKI progression in vivo by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Oral administration of SSNPs in mice resulted in absorption into the bloodstream, formation of a protein corona, reduced macrophage phagocytosis, and enhanced bioavailability and renal targeting. Furthermore, we investigated the self-assembly principle of SSNPs using representative flavonoids and terpenoids. Kinetic studies and in situ transmission electron microscopy (in situ TEM) revealed that these compounds self-assemble via supramolecular forces like hydrogen bonding and π-π interactions, forming stable nanostructures. This study elucidates the renoprotective effects and mechanisms of SB and SD, and provides a novel approach for the development of TCM-based nanomedicines, highlighting the potential of nano-TCM in AKI treatment.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

OBJECTIVE Based on the Heracles NEO ultra-fast gas phase electronic nose,to analyze the odor composition of Abutili Semen before and after stir-frying,and to establish an effective and rapid identification method of raw and stir-frying Abutili Se-men based on odor.METHODS The decoction pieces of Abutili Semen were prepared by stir-frying method.An ultra-fast gas-phase electronic nose method was established for the detection of Abutili Semen before and after stir-frying,the odor spectrum was col-lected,and the possible odor components and chromatographic peak areas were obtained in combination with the AroChemBase data-base,and analyzed by chemometric model.RESULTS The odor fingerprints of Abutili Semen before and after stir-frying were estab-lished,and 19 odor peaks were matched between Abutili Semen decoction pieces and stir-fried Abutili Semen.The peak areas of 7 odor components,hexanal,2-furanmethanol,2-methyl-2-propanol,2-methylbutanal,3-methylbutanal,2-methylpropanal,2,3,5-trim-ethylpyrazine,all increased after stir-frying,and the VIP values of the peaks were greater than 1(P<0.05),which were presumed to be the markers for the differences in the odors of Abutili Semen before and after stir-frying.CONCLUSION The Heracles NEO ul-tra-fast gas phase electronic nose can quickly identify the odor components of Abutili Semen before and after frying,which can provide new ideas and methods for quality control of Abutili Semen.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

Objective To explore the correlation between serum vitamin D(VD3)level differences and immune inflammatory markers in elderly sepsis patients.Methods A total of 103 elderly patients with sepsis(aged 65-99 years)in the ICU of the First Affiliated Hospital of Kunming Medical University from January 2020 to December 2022 were collected and divided into two groups according to the diagnostic criteria for VD3 deficiency:VD3 deficiency group(n=32)and VD3 severe deficiency group(n=71).Correlation analysis was conducted by comparing the differences in serum 25-(OH)-D3(VD3)levels,immune function-related indicators upon admission(blood routine,infection-related proteins,combined detection of 12 cytokines,absolute count analysis of lymphocytes and subgroups,quantitative determination of infection-related immune cells,immunoglobulin,and complement),illness severity,and prognostic indicators(APACHE-II score,SOFA score,duration of ICU stay,and 28-day mortality rate).Result(1)Serum VD3 levels were lower in elderly patients with sepsis.No patient was in the VD3 normal or insufficient group.Patients with severe VD3 deficiency had higher APACHE-II scores,SOFA scores,and 28-day mortality rates than those with VD3 deficiency,and these scores were negatively correlated with serum VD3 levels(P<0.001),while the difference in ICU stay duration between the two groups was not statistically significant(P>0.05);(2)WBC,PCT,CRP,and CD4/CD8 in the VD3 deficiency group were all lower than those in the VD3 severe deficiency group(P<0.05),while IL-6,IL-10,CD45+,CD3+/CD45+,and CD19+Abs were all higher than those in the VD3 severe deficiency group(P<0.05);In the VD3 deficiency group,VD3 levels were positively correlated with CD45+(P<0.05 for all),while negatively correlated with IL-6,IL-10,PCT,and CRP(P<0.05 for all);In the VD3 severe deficiency group,there were fewer corre-lation indicators and the correlation strength was not as strong as that in the VD3 deficiency group.Conclusion(1)Elderly patients with sepsis generally have lower levels of VD3,with lower levels associated with more severe illness and poorer prognosis;(2)In elderly sepsis patients,compared to patients with severe VD3 deficiency,patients with VD3 deficiency have lower levels of inflammation,stronger cellular immune response,and stronger correlation,suggesting that the effects of different VD3 levels on immune inflammatory responses may vary in elderly sepsis patients.

Objective : To investigate the expression and biological function of circular RNA(circRNA) hsa＿circ＿0002938 in gastric cancer. Methods : 45 pairs of tumor tissues and para-cancerous tissues from gastric cancer patients who underwent tumor reduction surgery at the hospital were collected. Human gastric cancer cells SGC-7901, BGC-823, HGC-27, MGC-803 and immortalized gastric mucosal epithelial cells GES-1 were routinely cultured. RT-qPCR was utilized to detect the expression of hsa＿circ＿0002938 in gastric cancer tissues and cells. Chi-square test was used to analyze its association with the clinicopathological characteristics of patients, and the Kaplan-Meier method was employed to assess the relationship between hsa＿circ＿0002938 expression levels and patient prognosis. The effects of hsa＿circ＿0002938 on the proliferation, migration and invasion abilities of gastric cancer cells were detected by CCK-8, scratch wound healing and Transwell assays. Bioinformatics was used to predict the miRNA and its downstream target genes that hsa＿circ＿0002938 might bind to. The competitive endogenous RNA regulatory network was constructed and the functions of the target genes were enriched. Results : The expression of hsa＿circ＿0002938 in gastric cancer tissues and cells was much higher than that in para-cancerous tissues and GES-1 cells(P<0.05). By contrast, patients in the high hsa＿circ＿0002938 expression group had significantly shorter 2-year progression-free survival than that in the low expression group after surgery(P<0.01). Moreover, knocking down the expression of hsa＿circ＿0002938 reduced the proliferative, migratory, and invasive abilities of gastric cancer cells(P<0.05). Bioinformatics predictive analysis showed that hsa＿circ＿0002938 could bind to hsa-miR-342-3p and hsa-miR-503-5p. The downstream target genes of miRNA were involved in several cancer-related pathways, like mitogen-activated protein kinase(MAPK), hippo and Wnt signaling pathway. Conclusion Hsa＿circ＿0002938, which is highly expressed in gastric cancer tissues and cells, is closely associated with poor patient prognosis. Knockdown of hsa＿circ＿0002938 inhibits the proliferation, migration, and invasion abilities of gastric cancer cells. The study reveals the potential role of hsa＿circ＿0002938 in the progression of gastric cancer, offering new insights into its prevention and treatment.

Objective To explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.

Objective To investigate the clinical characteristics of lower respiratory tract infections oc-currence and respiratory system prognosis in infantile stage of children patients with bronchopulmonary dys-plasia(BPD).Methods Fifty premature infants with lower respiratory tract infection and BPD treated in this hospital from March 2017 to December 2020 were selected as the BPD group and 50 preterm infants with low-er respiratory tract infection without BPD during the same period were selected as the non-BPD group.The clinical data and occurrence situation of respiratory system diseases within 3 years after birth in the two groups were collected and analyzed.Results Compared with the non-BPD group,the incidence rates of tachy-pnoea(48.0%vs.12.0%),wheeze(44.0%vs.10.0%),wheezing rale(44.0%vs.10.0%),three concave sign(28.0%vs.8.0%),cyanosis(20.0%vs.4.0%),severe pneumonia(48.0%vs.12.0%)and respirato-ry failure(20.0%vs.4.0%)in the BPD group were higher,the hospitalization duration[7.5(7.0,10.0)d vs.7.0(6.0,7.0)d]was longer,the reaching peak time ratio[18.20%(14.65%,22.25%)vs.24.85%(19.55%,32.78%)],the reaching peak volume ratio[22.15%(19.43%,23.83%)vs.25.65%(22.40%,34.90%)]and the inspiratory/expiratory ratio(0.70±0.12 vs.0.76±0.11)were lower,the 3-year total lower respiratory tract infection times[5.0(4.0,10.0)times vs.3.0(2.0,5.0)times],wheeze times[2.0(1.0,4.0)times vs.0.5(0,1.0)times],the hospitalization times[3.00(2.00,5.00)times vs.2.00(1.00,2.00)times],severe pneumonia times[2.0(1.0,2.0)times vs.1.0(0,1.0)times]and wheeze times in differ-ent ages were more,total hospitalization duration[29.50(19.50,38.25)d vs.13.00(7.00,17.75)d]was lon-ger,the differences were statistically significant(P<0.05).Conclusion The children patients with BPD are prone to lower respiratory tract infections,especially 0-<1 years old,the proportion of severe pneumonia af-ter infection is higher and wheezing is easily to develop.

Objective To explore the role of mitophagy in pancreatic cancer cachexia-induced muscle atrophy and its underlying mechanism.Methods Six male C57BL/6J mice(8 weeks old,weighing 20～30 g)were equally and randomly divided into a control group(intrapancreatic injection of normal saline)and a cachexia group(orthotopic pancreatic injection of KPC1199 cells).After successful model establishment,gastrocnemius muscles were harvested for transmission electron microscopy(TEM)to assess mitochondrial ultrastructure.Western blotting was performed to quantify mitochondrial respiratory chain complexes(Ⅰ～Ⅳ)and autophagy-related proteins,while immunofluorescence staining was conducted to evaluate mitochondrial-lysosomal colocalization.In in vitro experiments,C2C12 myoblasts were differentiated into myotubes,and then divided into a control group(standard culture)and a cachexia group(co-cultured with KPC1199 cells for 48 h using transwell chambers).Mitochondrial-lysosomal colocalization and autophagy-related protein expression were analyzed with immunofluorescence assay and Western blotting.The mitochondrial division inhibitor Mdivi-1(20 μmol/L)was added to the co-culture system to assess its myotube diameter.Results Compared to the control mice,the cachectic mice exhibited mitochondrial swelling,reduced cristae density,and significantly increased mitochondrial-lysosomal colocalization in gastrocnemius muscle(P<0.05).Western blotting revealed the expression levels of mitochondrial respiratory chain proteins complexⅠ(1.00±0.04 vs 0.51±0.04,P<0.05),complexⅡ(1.00±0.13 vs 0.73±0.15,P<0.05),complexⅢ(1.00±0.20 vs 0.64±0.01,P<0.05),complexⅣ(1.00±0.06 vs 0.65±0.02,P<0.05)and PGC1α(1.00±0.03 vs 0.62±0.06,P<0.05)were decreased,and the levels of mitophagy markers,LC3-Ⅰ/Ⅱ(1.00±0.14 vs 1.65±0.25,P<0.05),PINK1(1.00±0.11 vs 1.51±0.05,P<0.05),and BNIP3(1.00±0.22 vs 2.02±0.10,P<0.05)were elevated when compared to the control.In the C2C12 myotube model,tumor cell co-culture increased mitochondrial-lysosomal colocalization and upregulated mitophagy-related protein expression(P<0.05),consistent with the in vivo findings.Mdivi-1 treatment increased myotube diameter from 220.6±35.5 μm to 315.0±39.1 μm(R2=0.666 5,P<0.05).Conclusion Mitophagy is activated in pancreatic cancer cachexia-induced muscle atrophy.Inhibiting mitophagy can effectively alleviate muscle atrophy induced by pancreatic cancer cachexia.