Efficacy and safety of the S1PR modulator etrasimod in the treatment of moderately to severely active ulcerative colitis during the induction phase: a systematic review and meta-analysis of randomized controlled trials.

Background: The study aims to assess the efficacy and safety of the recently approved S1PR modulator etrasimod in adults with ulcerative colitis during the induction phase through meta-analysis. Methods: A systemic search was performed for randomized controlled trials evaluating the efficacy and safety of the S1PR modulator etrasimod using electronic databases PubMed, Embase, the Cochrane Library, Clinical Trials, and the International Clinical Trials Registry Platform. Three studies with 943 patients met the inclusion criteria and were included in this analysis. The study's primary endpoint was the proportion of patients who achieved clinical remission at week 12. Key secondary endpoints included the proportion of patients with clinical response, endoscopic improvement, and histologic remission. The incidence of adverse effects (AEs), serious AEs (SAEs), and AE-related treatment discontinuation were statistically analyzed to determine the safety of etrasimod. Results: This study revealed that etrasimod is superior to placebo at the primary endpoint clinical remission (OR = 3.09, 95% CI: 2.04-4.69), as well as at the secondary endpoints clinical response (OR = 2.56, 95% CI: 1.91-3.43), endoscopic improvement (OR = 2.15, 95% CI: 1.51-3.05), and histologic remission (OR = 3.39, 95% CI: 2.03-5.68). The proportion of patients with TEAE (OR = 1.34, 95% CI: 1.01-1.78) and SAE (OR = 0.77, 95% CI: 0.41-1.43) was similar between the etrasimod and placebo groups. Patients receiving etrasimod had slightly higher odds of experiencing headache (OR = 2.07, 95% CI: 1.01-4.23), and nausea (OR = 1.84, 95% CI: 0.72-4.72). The incidences of upper respiratory tract infection (OR = 0.79, 95% CI: 0.27-2.32), nasopharyngitis (OR = 0.40, 95% CI: 0.15-1.07), and urinary tract infection (OR = 1.82, 95% CI: 0.59-5.60) were generally lower in the etrasimod groups and no treatment-related serious infections were reported. Conclusion: This study demonstrates that etrasimod is effective in treating moderately to severely active ulcerative colitis with a favorable benefit-risk profile at week 12. Etrasimod shows promise as a potential first-line oral therapy for individuals suffering from this disease. Additional RCTs with larger sample sizes and longer observation periods are needed to confirm the sustained efficacy of etrasimod beyond the initial phase.

[Constructing an indexing template for ancient acupuncture medical cases based on knowledge element theory].

Ancient acupuncture medical cases not only possess historical literary value but also hold significant clinical importance. To enhance the utilization of ancient acupuncture medical cases and to guide the excavation of acupuncture theory and its clinical application, this study constructs an indexing template for "Ancient Acupuncture Medical Cases" based on the knowledge element theory and the fine-grained indexing requirements of ancient acupuncture texts. This template includes two levels, 7 categories, 28 knowledge element data, 31 semantic types, and 15 semantic relationships. These element data construct the interconnections of knowledge in ancient acupuncture medical cases, serving as a basis for fine-grained indexing of acupuncture medical case literature.

Effect of prehabilitation exercises on postoperative frailty in patients undergoing laparoscopic colorectal cancer surgery.

Background: To improve perioperative frailty status in patients undergoing laparoscopic colorectal cancer surgery (LCCS), we explored a new intensive prehabilitation program that combines prehabilitation exercises with standard enhanced recovery after surgery (ERAS) and explored its impact. Methods: We conducted a prospective randomized controlled trial. Between April 2021 to August 2021, patients undergoing elective LCCS were randomized into the standardized ERAS (S-ERAS) group or ERAS based on prehabilitation (group PR-ERAS). Patients in the PR-ERAS group undergoing prehabilitation exercises in the perioperative period in addition to standard enhanced recovery after surgery. We explored the effects of this prehabilitation protocol on frailty, short-term quality of recovery (QoR), psychological status, postoperative functional capacity, postoperative outcomes, and pain. Results: In total, 125 patients were evaluated, and 95 eligible patients were enrolled and randomly allocated to the S-ERAS (n = 45) and PR-ERAS (n = 50) groups. The Fried score was higher in the PR-ERAS group on postoperative day (7 (2(2,3) vs. 3(2,4), P = 0.012). The QoR-9 was higher in the PR-ERAS group than in the S-ERAS group on the 1st, 2nd, 3rd, and 7th postoperative days. The PR-ERAS group had an earlier time to first ambulation (P < 0.050) and time to first flatus (P < 0.050). Conclusion: Prehabilitation exercises can improve postoperative frailty and accelerate recovery in patients undergoing LCCS but may not improve surgical safety. Therefore, better and more targeted prehabilitation recovery protocols should be explored. Clinical trial registration: www.clinicaltrials.org , identifier NCT04964856.

PhIP-Seq: methods, applications and challenges.

Phage-immunoprecipitation sequencing (PhIP-Seq) technology is an innovative, high-throughput antibody detection method. It enables comprehensive analysis of individual antibody profiles. This technology shows great potential, particularly in exploring disease mechanisms and immune responses. Currently, PhIP-Seq has been successfully applied in various fields, such as the exploration of biomarkers for autoimmune diseases, vaccine development, and allergen detection. A variety of bioinformatics tools have facilitated the development of this process. However, PhIP-Seq technology still faces many challenges and has room for improvement. Here, we review the methods, applications, and challenges of PhIP-Seq and discuss its future directions in immunological research and clinical applications. With continuous progress and optimization, PhIP-Seq is expected to play an even more important role in future biomedical research, providing new ideas and methods for disease prevention, diagnosis, and treatment.

Identifying subtypes of Type 2 diabetes mellitus based on real-world electronic medical record data in China.

AIMS: To replicate the European subtypes of type 2 diabetes mellitus (T2DM) in Chinese diabetes population, and investigate the risk of complications in different subtypes. METHODS: A diabetes cohort using real-world patient data was constructed and clustering was employed to subgroup the T2DM patients. Kaplan-Meier analysis and the Cox model were used to analyze the association between diabetes subtypes and the risk of complications. RESULTS: A total of 2,652 T2DM patients with complete clustering data were extracted. Among them, 466 (17.57 %) were classified as severe insulin-deficient diabetes (SIDD), 502 (18.93 %) as severe insulin-resistant diabetes (SIRD), 672 (25.34 %) as mild obesity-related diabetes (MOD), and 1,012 (38.16 %) as mild age-related diabetes (MARD). The risk of chronic kidney disease (CKD) and diabetic retinopathy (DR) were different in the four subtypes. Compared with MARD, SIRD had a higher risk of CKD (HR 2.01 [1.03, 3.91]), and SIDD had a higher risk of DR (HR 2.17 [1.12, 4.20]). The risk of stroke and coronary events had no difference. CONCLUSIONS: The European T2DM subtypes can be replicated in Chinese diabetes population. The risk of CKD and DR varied among different subtypes, indicating that proper interventions can be taken to prevent specific complications in different subtypes.

Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer's disease.

Although autosomal-dominant inheritance is believed an important cause of familial clustering Alzheimer's disease (FAD), it covers only a small proportion of FAD incidence, and so we investigated epigenetic memory as an alternative mechanism to contribute for intergenerational AD pathogenesis. Our data in vivo showed that mys-2 of Caenorhabditis elegans that encodes a putative MYST acetyltransferase responsible for H4K16 acetylation modulated AD occurrence. The phenotypic improvements in the parent generation caused by mys-2 disfunction were passed to their progeny due to epigenetic memory, which resulted in similar H4K16ac levels among the candidate target genes of MYS-2 and similar gene expression patterns of the AD-related pathways. Furthermore, the ROS/CDK-5/ATM pathway functioned as an upstream activator of MYS-2. Our study indicated that MYS-2/MOF could be inherited intergenerationally via epigenetic mechanisms in C. elegans and mammalian cell of AD model, providing a new insight into our understanding of the etiology and inheritance of FAD.

Case report: A rare case of malignant solitary fibrous tumor in an adult with an epithelioid pattern in the occipital region.

We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy.

VPS34 Governs Oocyte Developmental Competence by Regulating Mito/Autophagy: A Novel Insight into the Significance of RAB7 Activity and Its Subcellular Location.

Asynchronous nuclear and cytoplasmic maturation in human oocytes is believed to cause morphological anomalies after controlled ovarian hyperstimulation. Vacuolar protein sorting 34 (VPS34) is renowned for its pivotal role in regulating autophagy and endocytic trafficking. To investigate its impact on oocyte development, oocyte-specific knockout mice (ZcKO) are generated, and these mice are completely found infertile, with embryonic development halted at 2- to 4-cell stage. This infertility is related with a disruption on autophagic/mitophagic flux in ZcKO oocytes, leading to subsequent failure of zygotic genome activation (ZGA) in derived 2-cell embryos. The findings further elucidated the regulation of VPS34 on the activity and subcellular translocation of RAS-related GTP-binding protein 7 (RAB7), which is critical not only for the maturation of late endosomes and lysosomes, but also for initiating mitophagy via retrograde trafficking. VPS34 binds directly with RAB7 and facilitates its activity conversion through TBC1 domain family member 5 (TBC1D5). Consistent with the cytoplasmic vacuolation observed in ZcKO oocytes, defects in multiple vesicle trafficking systems are also identified in vacuolated human oocytes. Furthermore, activating VPS34 with corynoxin B (CB) treatment improved oocyte quality in aged mice. Hence, VPS34 activation may represent a novel approach to enhance oocyte quality in human artificial reproduction.

CALR3 defects disrupt sperm-zona pellucida binding in humans: new insights into male factor fertilization failure and relevant clinical therapeutic approaches.

STUDY QUESTION: Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans? SUMMARY ANSWER: Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding. WHAT IS KNOWN ALREADY: In male mice, the Calr3-knockout has been reported to cause male infertility and FF. However, the mechanism behind this remains unclear in humans. STUDY DESIGN, SIZE, DURATION: Sequencing studies were conducted in a research hospital on samples from Han Chinese families with primary infertility and sperm head deformations to identify the underlying genetic causes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from two infertile probands characterized by sperm head deformation were collected through in silico analysis. Sperm cells from the probands were characterized using light and electron microscopy and used to verify the pathogenicity of genetic factors through functional assays. Subzonal insemination (SUZI) and IVF assays were performed to determine the exact pathogenesis of FF. ICSI were administered to overcome CALR3-affected male infertility. MAIN RESULTS AND THE ROLE OF CHANCE: Novel biallelic deleterious mutations in CALR3 were identified in two infertile men from unrelated families. We found one homozygous frameshift CALR3 mutation (M1: c.17_27del, p.V6Gfs*34) and one compound heterozygous CALR3 mutation (M2: c.943A>G, p.N315D; M3: c.544T>C, p.Y182H). These mutations are rare in the general population and cause acrosomal ultrastructural defects in affected sperm. Furthermore, spermatozoa from patients harbouring the CALR3 mutations were unable to bind to the sperm-ZP or they disrupted gamete fusion or prevented oocyte activation. Molecular assays have revealed that CALR3 is crucial for the maturation of the ZP binding protein in humans. Notably, the successful fertilization via SUZI and ICSI attempts for two patients, as well as the normal expression of PLCζ in the mutant sperm, suggests that ICSI is an optimal treatment for CALR3-deficient FF. LIMITATIONS, REASONS FOR CAUTION: The results are based on sperm-related findings from two patients. Further studies are required to gain insight into the developmental stage and function of CALR3 in human testis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the underlying risk of FF associated with sperm defects and provide a valuable reference for personalized genetic counselling and clinical treatment of these patients. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key R&D Program of China (2021YFC2700901), Hefei Comprehensive National Science Center Medical-Industrial Integration Medical Equipment Innovation Research Platform Project (4801001202), the National Natural Science Foundation of China (82201803, 82371621, 82271639), Foundation of the Education Department of Anhui Province (gxgwfx2022007), Key Project of Natural Science Research of Anhui Educational Committee (2023AH053287), and the Clinical Medical Research Transformation Project of Anhui Province (202204295107020037). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Vascular Calcification: Where is the Cure?

With the progress of aging, the incidence of vascular calcification (VC) gradually increases, which is correlated with cardiovascular events and all-cause death, aggravating global clinical burden. Over the past several decades, accumulating approaches targeting the underlying pathogenesis of VC have provided some possibilities for the treatment of VC. Unfortunately, none of the current interventions have achieved clinical effectiveness on reversing or curing VC. The purpose of this review is to make a summary of novel perspectives on the interventions of VC and provide reference for clinical decision-making.

Sappanone A enhances hepatocyte proliferation in lipopolysaccharide-induced acute liver injury in mice by promoting injured hepatocyte apoptosis and regulating macrophage polarization.

OBJECTIVES: Lipopolysaccharide (LPS), also known as endotoxin, is the main toxic component of the cell wall of gram negative bacteria, which is released after bacterial death and widely exists in the living environment. Human exposure to endotoxin may cause sepsis. The occurrence of septic liver injury is a prominent factor contributing to mortality in patients with sepsis. The purpose of this study is to explore the role of Sappanone A (SA), a homoisoflavonoid isolated from the heartwood of Caesalpinia sappan Linn., in LPS-induced acute liver injury (ALI). METHODS: An LPS-induced ALI mouse model was used to evaluate the effects of SA on septic ALI, and murine cells were treated with LPS to explore the mechanisms underlying SA-provided effects. RESULTS: Treating SA substantially improved LPS-induced ALI. We also performed in silico prediction and RNA-seq analysis to elucidate SA's potential mechanisms of action. The terms generated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of predicted target proteins of SA include inflammation, oxidative stress, and apoptosis; protein-protein interaction network (PPI) analysis indicated that fas binding protein 1 (Fbf1) has the strongest correlation with SA. Consistently, RNA-seq analysis displayed that SA administration regulates cell apoptosis and inflammatory responses, which was further confirmed by checking related markers in livers of mice and murine cells challenged with LPS. Of note, SA significantly decreased the expression of Fbf1 in mouse livers, and promoted apoptosis of injured hepatocytes and hepatocyte proliferation, which were substantially abolished by Fbf1 knockdown in AML12 cells. Besides, SA could increase M2 phenotype polarization but inhibit M1 macrophage polarization in LPS-induced ALI in mice. CONCLUSION: SA enhances hepatocyte proliferation and liver repair in LPS-induced ALI in mcie by promoting injured hepatocyte apoptosis through Fbf1 inhibition and regulating macrophage polarization.

Integrative genomics reveals the polygenic basis of seedlessness in grapevine.

Seedlessness is a crucial quality trait in table grape (Vitis vinifera L.) breeding. However, the development of seeds involved intricate regulations, and the polygenic basis of seed abortion remains unclear. Here, we combine comparative genomics, population genetics, quantitative genetics, and integrative genomics to unravel the evolution and polygenic basis of seedlessness in grapes. We generated the haplotype-resolved genomes for two seedless grape cultivars, "Thompson Seedless" (TS, syn. "Sultania") and "Black Monukka" (BM). Comparative genomics identified a ∼4.25 Mb hemizygous inversion on Chr10 specific in seedless cultivars, with seedless-associated genes VvTT16 and VvSUS2 located at breakpoints. Population genomic analyses of 548 grapevine accessions revealed two distinct clusters of seedless cultivars, and the identity-by-descent (IBD) results indicated that the origin of the seedlessness trait could be traced back to "Sultania." Introgression, rather than convergent selection, shaped the evolutionary history of seedlessness in grape improvement. Genome-wide association study (GWAS) analysis identified 110 quantitative trait loci (QTLs) associated with 634 candidate genes, including previously unidentified candidate genes, such as three 11S GLOBULIN SEED STORAGE PROTEIN and two CYTOCHROME P450 genes, and well-known genes like VviAGL11. Integrative genomic analyses resulted in 339 core candidate genes categorized into 13 functional categories related to seed development. Machine learning-based genomic selection achieved a remarkable prediction accuracy of 97% for seedlessness in grapevines. Our findings highlight the polygenic nature of seedlessness and provide candidate genes for molecular genetics and an effective prediction for seedlessness in grape genomic breeding.

FOXO1-NCOA4 Axis Contributes to Cisplatin-Induced Cochlea Spiral Ganglion Neuron Ferroptosis via Ferritinophagy.

Mammalian cochlea spiral ganglion neurons (SGNs) are crucial for sound transmission, they can be damaged by chemotherapy drug cisplatin and lead to irreversible sensorineural hearing loss (SNHL), while such damage can also render cochlear implants ineffective. However, the mechanisms underlying cisplatin-induced SGNs damage and subsequent SNHL are still under debate and there is no currently effective clinical treatment. Here, this study demonstrates that ferroptosis is triggered in SGNs following exposure to cisplatin. Inhibiting ferroptosis protects against cisplatin-induced SGNs damage and hearing loss, while inducing ferroptosis intensifies these effects. Furthermore, cisplatin prompts nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in SGNs, while knocking down NCOA4 mitigates cisplatin-induced ferroptosis and hearing loss. Notably, the upstream regulator of NCOA4 is identified and transcription factor forkhead box O1 (FOXO1) is shown to directly suppress NCOA4 expression in SGNs. The knocking down of FOXO1 amplifies NCOA4-mediated ferritinophagy, increases ferroptosis and lipid peroxidation, while disrupting the interaction between FOXO1 and NCOA4 in NCOA4 knock out mice prevents the cisplatin-induced SGN ferroptosis and hearing loss. Collectively, this study highlights the critical role of the FOXO1-NCOA4 axis in regulating ferritinophagy and ferroptosis in cisplatin-induced SGNs damage, offering promising therapeutic targets for SNHL mitigation.

[Emission Characteristics and Environmental Impact of VOCs from Wooden Furniture-manufacturing Industry in China].

Volatile organic compounds （VOCs） from the wooden furniture-manufacturing industry are an important emission source. To study the emission characteristics of VOCs from the wooden furniture-manufacturing industry and associated environmental impacts, nine typical wooden furniture manufacturers in China were selected to carry out sample collection and VOCs detection. The maximum incremental reactivity （MIR） method and secondary organic aerosol （SOA） formation potential method were used to quantify the corresponding contributions to the generation of O3 and SOA. The results showed that： ① The concentrations of VOCs emitted from different types of coating exhaust gas were different. The emission concentration of VOCs in solvent-based coating exhaust gas was significantly higher than that in water-based coating exhaust gas and ultra-violet （UV） coating exhaust gas, and the VOCs emission concentrations ranged between 2.82 - 155.37, 1.13 - 104.45, and 0.57 - 1.15 mg·m-3, respectively. ② The main organic group in solvent-based coating exhaust gas was esters, accounting for 45.88%, and butyl acetate （31.07%） was the main VOCs species. The main organic group in water-based coating exhaust gas and UV coating exhaust gas was alcohols, and the main VOCs species in water-based coating exhaust gas and UV coating exhaust gas were both ethanol, accounting for 46.63% and 34.32%, respectively. ③ The OFP of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 149.23, 50.90, and 1.87 mg·m-3, respectively, and the primary contributing components of OFP of different types of coating were m/p-xylene （26.61%）, ethanol （36.35%）, and ethanol （23.98%）, respectively. ④ The SOA of VOCs emitted by solvent-based coating, water-based coating, and UV coating were 0.76, 0.25, and 0.01 mg·m-3, respectively. The SOA generation of various types of coating was dominated by aromatics（96.35%-98.96%）, and the main active compounds were toluene, ethylbenzene, and xylene. ⑤ Comparing the environmental impact of exhaust gas from solvent-based coating, water-based coating, and UV coating, it was found that the OFP and SOA generated by the VOCs emitted from solvent-based coating were much higher than those for water-based coating and UV coating. Therefore, the implementation of water-based coating and UV coating substitution strategy from the source could effectively reduce VOCs emissions and abate OFP and SOA productions.

Early oral hydration on demand in postanesthesia care unit effectively relieves postoperative thirst in patients after gynecological laparoscopy: a prospective randomized controlled trial.

BACKGROUND: Postoperative thirst is one of the most intense, common and easily ignored subjective discomforts in patients after gynecological surgery. This study aimed to investigate whether early oral hydration on demand in the postanesthesia care unit (PACU) after gynecological laparoscopy under general anesthesia can appease postoperative thirst and increase patient comfort. METHODS: Participants were randomized into the intervention and control groups. Patients in the intervention group were allowed to achieve early oral hydration on demand in the PACU if they were evaluated as fully conscious, with stable vital signs, grade 5 muscle strength, and well-recovered cough and swallowing reflex. However, the total amount of water intake throughout the entire study should not exceed 0.5mL/kg. During the study, the frequency of water intake, the total amount of water intake and adverse events were accurately recorded. The control group was managed according to the routine procedures and began to drink water 2 h after anesthesia. The intensity of thirst and subjective comfort in patients were assessed using the visual analog scale (VAS) when they entered and left the PACU. RESULTS: No statistically significant differences were identified in age, height, weight, body mass index, pre-operative fasting time, duration of surgery, intraoperative fluid intake, intraoperative blood loss, intraoperative urine volume, and thirst intensity and subjective comfort scores between the groups before intervention (P > 0.05). After intervention, the VAS score for thirst intensity in the intervention group significantly decreased (P < 0.05), and the VAS score for subjective comfort in the intervention group significantly increased (P < 0.05). No adverse events were detected in both groups during the entire study. CONCLUSION: Early oral hydration on demand in the PACU can safely and effectively relieve postoperative thirst in patients, and improve patient comfort after gynecological laparoscopy. TRIAL REGISTRATION: This single-center, prospective, randomized controlled trial was registered at the Chinese Clinical Trial Center on April 27, 2023. The registration number of this study is ChiCTR2300070985.

Reactive astrocytes promote tumor progression by up-regulating tumor protocadherin 1 expression in lung cancer brain metastasis.

Brain metastasis (BM) is one of the main causes of death in patients with non-small cell lung carcinoma. The specific pathological processes of BM, which are inextricably linked to the brain tumor microenvironment, such as the abundance of astrocytes, lead to limited treatment options and poor prognosis. Reactive astrocytes are acquired in the BM; however, the underlying mechanisms remain unclear. This study aimed to explore the mechanisms by which astrocytes promote BM development. We determined the crucial role of reactive astrocytes in promoting the proliferation and migration of brain metastatic lung tumor cells by upregulating protocadherin 1 (PCDH1) expression in an in vitro co-culture model. The overexpression of PCDH1 was confirmed in clinical BM samples using immunohistochemical staining. Survival analysis indicated that high-PCDH1 expression was associated with poor survival in patients with lung adenocarcinoma. In vivo assays further showed that silence of PCDH1 effectively inhibited the tumor progression of brain metastases and prolonged the survival of animals. RNA sequencing has revealed that PCDH1 plays an important role in cell proliferation and adhesion. In conclusion, the present study revealed the promoting role of astrocytes in enhancing the aggressive phenotype of brain metastatic tumor cells by regulating the expression of PCDH1, which might be a biomarker for BM diagnosis and prognosis, suggesting the potential efficacy of targeting important astrocyte-tumor interactions in the treatment of patients with non-small cell lung carcinoma with BM.

A Senomorphlytic Three-Drug Combination Discovered in Salsola collina for Delaying Aging Phenotypes and Extending Healthspan.

The pursuit of pharmacological interventions in aging aims focuses on maximizing safety and efficacy, prompting an exploration of natural products endowed with inherent medicinal properties. Subsequently, this work establishes a unique library of plant extracts sourced from Yunnan Province, China. Screening of this herbal library herein revealed that Salsola collina (JM10001) notably enhances both lifespan and healthspan in C. elegans. Further analysis via network pharmacology indicates that the p53 signaling pathway plays a crucial role in mediating the anti-aging effects of JM10001. Additionally, this work identifies that a composition, designated as JM10101 and comprising three chemical constituents of JM10001, preserves the original lifespan-extending activity in C. elegans. Both JM10001 and JM10101 mitigate aging symptoms in senescence-accelerated mice treated with doxorubicin and in naturally aged mice. Notably, JM10101 exhibits a more sophisticated senomorphlytic role encompassing both senomorphic and senolytic functions than JM10001 in the modulation of senescent cells, offering a promising strategy for the discovery of combination drugs in the rational development of anti-aging therapies.

Long-term ultraviolet B irradiation at 297†nm with light-emitting diode improves bone health via vitamin D regulation.

Ultraviolet radiation is the primary determinant for vitamin D synthesis. Sunlight is inefficient and poses a risk, particularly for long-term exposure. In this study, we screened the most favorable wavelength for vitamin D synthesis among four types of narrowband light-emitting diodes (LEDs) and then irradiated osteoporosis rats with the optimal wavelength for 3-12 months. The 297 nm narrowband LED was the most efficient. Long-term radiation increased vitamin D levels in all osteoporotic rats and improved bone health. No skin damage was observed during irradiation. Our findings provide an efficient and safe method of vitamin D supplementation.

Limited life-history plasticity in marginal population of an invasive foundation species: Unraveling the genetic underpinnings and ecological implications.

Plant's life history can evolve in response to variation in climate spatio-temporally, but numerous multiple-species studies overlook species-specific (especially a foundation species) ecological effects and genetic underpinnings. For a species to successfully invade a region, likely to become a foundation species, life-history variation of invasive plants exerts considerable ecological and evolutionary impacts on invaded ecosystems. We examined how an invasive foundation plant, Spartina alterniflora, varied in its life history along latitudinal gradient using a common gardens experiment. Two common gardens were located at range boundary in tropical zone and main distribution area of S. alterniflora in temperate zone in China. Within each population/garden, we measured the onset time of three successive phenological stages constituting the reproductive phase and a fitness trait. In the low-latitude garden with higher temperature, we found that reproductive phase was advanced and its length prolonged compared to the high-latitude garden. This could possibly due to lower plasticity of maturity time. Additionally, plasticity in the length of the reproductive phase positively related with fitness in the low-latitude garden. Marginal population from tropic had the lowest plasticity and fitness, and the poor capacity to cope with changing environment may result in reduction of this population. These results reflected genetic divergence in life history of S. alterniflora in China. Our study provided a novel view to test the center-periphery hypothesis by integration across a plant's life history and highlighted the significance in considering evolution. Such insights can help us to understand long-term ecological consequences of life-history variation, with implications for plant fitness, species interaction, and ecosystem functions under climate change.

Transfection of entomopathogenic Metarhizium species with a mycovirus confers hypervirulence against two lepidopteran pests.

Although most known viruses infecting fungi pathogenic to higher eukaryotes are asymptomatic or reduce the virulence of their host fungi, those that confer hypervirulence to entomopathogenic fungus still need to be explored. Here, we identified and studied a novel mycovirus in Metarhizium flavoviride, isolated from small brown planthopper (Laodelphax striatellus). Based on molecular analysis, we tentatively designated the mycovirus as Metarhizium flavoviride partitivirus 1 (MfPV1), a species in genus Gammapartitivirus, family Partitiviridae. MfPV1 has two double-stranded RNAs as its genome, 1,775 and 1,575 bp in size respectively, encapsidated in isometric particles. When we transfected commercial strains of Metarhizium anisopliae and Metarhizium pingshaense with MfPV1, conidiation was significantly enhanced (t test; P-value < 0. 01), and the significantly higher mortality rates of the larvae of diamondback moth (Plutella xylostella) and fall armyworm (Spodoptera frugiperda), two important lepidopteran pests were found in virus-transfected strains (ANOVA; P-value < 0.05). Transcriptomic analysis showed that transcript levels of pathogenesis-related genes in MfPV1-infected M. anisopliae were obviously altered, suggesting increased production of metarhizium adhesin-like protein, hydrolyzed protein, and destruxin synthetase. Further studies are required to elucidate the mechanism whereby MfPV1 enhances the expression of pathogenesis-related genes and virulence of Metarhizium to lepidopteran pests. This study presents experimental evidence that the transfection of other entomopathogenic fungal species with a mycovirus can confer significant hypervirulence and provides a good example that mycoviruses could be used as a synergistic agent to enhance the biocontrol activity of entomopathogenic fungi.