Molecular Mechanisms of Plant Extracts in Protecting Aging Blood Vessels.

Plant Extracts (PE) are natural substances extracted from plants, rich in various bioactive components. Exploring the molecular mechanisms and interactions involved in the vascular protective effects of PE is beneficial for the development of further strategies to protect aging blood vessels. For this review, the content was obtained from scientific databases such as PubMed, China National Knowledge Infrastructure (CNKI), and Google Scholar up to July 2024, using the search terms "Plant extracts", "oxidative stress", "vascular aging", "endothelial dysfunction", "ROS", and "inflammation". This review highlighted the effects of PE in protecting aging blood vessels. Through pathways such as scavenging reactive oxygen species, activating antioxidant signaling pathways, enhancing respiratory chain complex activity, inhibiting mitochondrial-reactive oxygen species generation, improving nitric oxide bioavailability, downregulating the secretion of inflammatory factors, and activating sirtuins 1 and Nrf2 signaling pathways, it can improve vascular structural and functional changes caused by age-related oxidative stress, mitochondrial dysfunction, and inflammation due to aging, thereby reducing the incidence of age-related cardiovascular diseases.

Clinical efficacy of Osteoking in knee osteoarthritis therapy: a prospective, multicenter, non-randomized controlled study in China.

Background: Osteoking has been extensively used for the treatment of knee osteoarthritis (KOA). However, it is lack of high-quality evidence on the clinical efficacy of Osteoking against KOA and the comparison with that of nonsteroidal anti-inflammatory drugs (NSAIDs). Aims: To evaluate the efficacy and safety of Osteoking in treating KOA. Methods: In the current study, a total of 501 subjects were recruited from 20 medical centers, and were divided into the Osteoking treatment group (n = 428) and the NSAIDs treatment group (n = 73). The Propensity Score Matching method was used to balance baseline data of different groups. Then, the therapeutic effects of Osteoking and NSAIDs against KOA were evaluated using VAS score, WOMAC score, EQ-5D-3L and EQ-VAS, while the safety of the two treatment were both assessed based on dry mouth, dizziness, diarrhea, etc. Results: After 8 weeks of treatment, the Osteoking group was compared with the NSAIDs group, the VAS score [2.00 (1.00, 3.00) vs. 3.00 (2.00, 4.00)], WOMAC pain score [10.00 (8.00, 13.00) vs. 11.00 (8.00, 16.00) ], WOMAC physical function score [32.00 (23.00, 39.00) vs. 39.07 ± 16.45], WOMAC total score [44.00 (31.00, 55.00) vs. 53.31 ± 22.47) ], EQ-5D-3L score [0.91 (0.73, 0.91) vs. 0.73 (0.63, 0.83) ] and EQ-VAS score [80.00 (79.00, 90.00) vs. 80.00 (70.00, 84.00) ] were improved by the treatment of Osteoking for 8 weeks more effectively than that by the treatment of NSAIDs. After 8 weeks of treatment with Osteoking, the VAS scores of KOA patients with the treatment of Osteoking for 8 weeks were reduced from 6.00 (5.00, 7.00) to 2.00 (1.00, 3.00) (p < 0.05), which was better than those with the treatment of NSAIDs starting from 2 weeks during this clinical observation. Importantly, further subgroup analysis revealed that the treatment of Osteoking was more suitable for alleviating various clinical symptoms of KOA patients over 65 years old, with female, KL II-III grade and VAS 4-7 scores, while the clinical efficacy of NSAIDs was better in KOA patients under 65 years old and with VAS 8-10 scores. Of note, there were no differences in adverse events and adverse reactions between the treatment groups of the two drugs. Conclusion: Osteoking may exert a satisfying efficacy in relieving joint pain and improving life quality of KOA patients without any adverse reactions, especially for patients with KL II-III grades and VAS 4-7 scores. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=55387, Identifier ChiCTR2000034475.

Global overview of anterior cruciate ligament reconstruction in children and adolescents over the past 20 years: a bibliometric analysis.

OBJECTIVES: The objectives of this paper is to conduct a bibliometric analysis to examine the research status and development trend of anterior cruciate ligament injury and reconstruction in children and adolescents over the past 20 years. DESIGN: Descriptive Research. METHODS: This study obtained information regarding studies on Anterior Cruciate Ligament Reconstruction in Children and Adolescents from the Web of Science Core Collection database. Visual and bibliometric analysis were conducted using VOSviewer, Origin 2022, Pajek64 5.18and Excel 2019. These analytic tools facilitated the analysis of various aspects, including countries/regions, institutions, authors, journals and keywords related to the research. RESULTS: From 2003 to 2023, a total of 1328 articles were retrieved in WOS, and 637 articles were selected by two authors. The most productive institutions are Childrens Hosp Philadelphia, Kocher, ms. Their articles have the highest number of publications and citations. The American journal of sports medicine is the most frequently cited journal for articles on anterior cruciate ligament reconstruction in children and adolescents. The most common keywords used in these articles were "anterior cruciate ligament reconstruction", "injury, children, adolescent", and "skeletally immature patients". CONCLUSIONS: This study provides valuable insights into the research focus of anterior cruciate ligament reconstruction in children and adolescents. In recent years, there has been significant attention paid to areas of "the return to sport, re-repture rate and functional recovery after anterior cruciate ligament reconstruction" in this specific population. These aspects have emerged as key directions for future research in this field.

TL1A Promotes Fibrogenesis in Colonic Fibroblasts via the TGF-ß1/Smad3 Signaling Pathway.

OBJECTIVE: Intestinal fibrosis is a refractory complication of inflammatory bowel disease (IBD). Tumor necrosis factor ligand-related molecule-1A (TL1A) is important for IBD-related intestinal fibrosis in a dextran sodium sulfate (DSS)-induced experimental colitis model. This study aimed to explore the effects of TL1A on human colonic fibroblasts. METHODS: A trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic (Tg) or wild-type (WT) mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis. The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell (PBMC) supernatant. The proliferation and activation of CCD-18Co cells were detected by BrdU assays, flow cytometry, immunocytochemistry and Western blotting. Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The level of collagen metabolism in the TNBS+ethyl alcohol (EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group. Transforming growth factor-ß1 (TGF-ß1) and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group. The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A, and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4% at 24 h. TL1A promoted cell activation and increased the levels of COL1A2, COL3A1, and TIMP-1 in CCD-18Co cells. Treatment of CCD-18Co cells with TL1A increased the expression of TGF-ß1 and p-Smad3. CONCLUSION: TL1A promotes TGF-ß1-mediated intestinal fibroblast activation, proliferation, and collagen deposition and is likely related to an increase in the TGF-ß1/Smad3 signaling pathway.

Visible-light-induced photocatalyst-free cascade cyclization of 3-(2-(ethynyl)phenyl)quinazolinones to sulfonated quinolino[2,1-b]quinazolinones.

A visible-light-induced K2S2O8-promoted cascade sulfonation/cyclization reaction was established using 3-(2-(ethynyl)phenyl)quinazolinones as efficient substrates under mild conditions. A series of sulfonated quinolino[2,1-b]quinazolinones were successfully synthesized under transition-metal- and photocatalyst-free conditions. Notably, this strategy has the advantages of room temperature and simple operation, easy scale-up, and good functional group tolerance.

METTL14 mediates nerve growth factor-stimulated testosterone synthesis in porcine theca cells.

Ovarian theca cells produce testosterone, which acts as a vital precursor substance for synthesizing estrogens during follicular development. Nerve growth factor (NGF) has been shown to participate in reproductive physiology, specifically to follicular development and ovulation. There is currently no available data on the impact of NGF on testosterone synthesis in porcine theca cells. Furthermore, m6A modification is the most common internal modification in eukaryotic mRNAs that are closely associated with female gametogenesis, follicle development, ovulation, and other related processes. It is also uncertain whether the three main enzymes associated with m6A, such as Writers, Erasers and Readers, play a role in this process. The present study, with an in vitro culture model, investigated the effect of NGF on testosterone synthesis in porcine theca cells and the role of Writers-METTL14 in this process. It was found that NGF activates the PI3K/AKT signaling pathway through METTL14, which regulates testosterone synthesis in porcine theca cells. This study will help to further elucidate the mechanisms by which NGF regulates follicular development and provide new therapeutic targets for ovary-related diseases in female animals.

Advances in regenerated cellulosic aerogel from waste cotton textile for emerging multidimensional applications.

Rapid development of society and the improvement of people's living standards have stimulated people's keen interest in fashion clothing. This trend has led to the acceleration of new product innovation and the shortening of the lifespan for cotton fabrics, which has resulting in the accumulation of waste cotton textiles. Although cotton fibers can be degraded naturally, direct disposal not only causes a serious resource waste, but also brings serious environmental problems. Hence, it is significant to explore a cleaner and greener waste textile treatment method in the context of green and sustainable development. To realize the high-value utilization of cellulose II aerogel derived from waste cotton products, great efforts have been made and considerable progress has been achieved in the past few decades. However, few reviews systematically summarize the research progress and future challenges of preparing high-value-added regenerated cellulose aerogels via dissolving cotton and other cellulose wastes. Therefore, this article reviews the regenerated cellulose aerogels obtained through solvent methods, summarizes their structure, preparation strategies and application, aimed to promote the development of the waste textile industry and contributed to the realization of carbon neutrality.

Heat stress-induced dysbiosis of the gut microbiota impairs spermatogenesis by regulating secondary bile acid metabolism in the gut.

Heat stress (HS) poses a substantial challenge to livestock. Studies have demonstrated that HS reduces fertility and leads to gut microbiota dysbiosis in bulls. However, the impact of the gut microbiota on fertility in bulls during HS is still unclear. Our research revealed that HS exposure decreased semen quality in bulls, and fecal microbiota transplantation (FMT) from heat-stressed bulls to recipient mice resulted in a significant decrease in number of testicular germ cells and epididymal sperm. Untargeted metabolomics methodology and 16S rDNA sequencing conjoint analysis revealed that Akkermansia muciniphila (A. muciniphila) seemed to be a key bacterial regulator of spermatogenesis after HS exposure. Moreover, the research indicated that A. muciniphila regulated secondary bile acid metabolism by promoting the colonization of bile salt hydrolase (BSH)-metabolizing bacteria, leading to increase of retinol absorption in the host gut and subsequently elevation of testicular retinoic acid level, thereby improving spermatogenesis. This study sheds light on the relationship between HS-induced microbiota dysbiosis and spermatogenesis, offering a potential therapeutic approach for addressing bull spermatogenic dysfunction triggered by HS exposure.

Exosomal long non-coding RNA AU020206 alleviates macrophage pyroptosis in atherosclerosis by suppressing CEBPB-mediated NLRP3 transcription.

Recent studies have suggested exosomes (EXO) as potential therapeutic tools for cardiovascular diseases, including atherosclerosis (AS). This study investigates the function of bone marrow stem cell (BMSC)-derived exosomes (EXO) on macrophage pyroptosis in AS and explores the associated mechanism. BMSC-EXO were isolated from healthy mice and identified. RAW264.7 cells (mouse macrophages) were exposed to oxLDL to simulate an AS condition. BMSC-EXO treatment enhanced viability and reduced lactate dehydrogenase release of macrophages. An animal model of AS was established using ApoE-/- mice. BMSC-EXO treatment suppressed plaque formation as well as macrophage and lipid infiltration in mouse aortic tissues. Moreover, BMSC-EXO decreased concentrations of pyroptosis-related markers interleukin (IL)-1ß, IL-18, cleaved-caspase-1 and gasdermin D in vitro and in vivo. Long non-coding RNA AU020206 was carried by the BMSC-EXO, and it bound to CCAAT enhancer binding protein beta (CEBPB) to block CEBPB-mediated transcriptional activation of NLR family pyrin domain containing 3 (NLRP3). Functional assays revealed that silencing of AU020206 aggravated macrophage pyroptosis and exacerbated AS symptoms in mice. These exacerbations were blocked upon CEBPB silencing but then restored after NLRP3 overexpression. In conclusion, this study demonstrates that AU020206 delivered by BMSC-EXO alleviates macrophage pyroptosis in AS by blocking CEBPB-mediated transcriptional activation of NLRP3.

Gut-Derived Exosomes Mediate the Microbiota Dysbiosis-Induced Spermatogenesis Impairment by Targeting Meioc in Mice.

Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non-reproductive tissue-originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single-cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR-211-5p in gut-derived circulating exosomes, which inhibited the expression of meiosis-specific with coiled-coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut-derived exosomes in connecting the "gut-testis" axis.

A triple-crosslinking strategy for high-performance regenerated cellulose fibers derived from waste cotton textiles.

Regenerated cellulose fibers has attracted increasing attention for high-grade textile raw materials and industrial textiles, but the low mechanical property caused by differences in regenerated raw materials and production levels limits its commercial application in the product diversity. Herein, we proposed a novel triple-crosslinking strategy by coupling with hydrogen bonds, chemical crosslinking, and internal mineralization from multiple pulsed vapor phase infiltration (MPI) to improve the mechanical performance of regenerated cellulose fibers. A binary solvent composed of ionic liquid (IL) and dimethyl sulfoxide (DMSO) is used to dissolve waste cotton textile and then wet spinning. Dual-crosslinking is firstly achieved by coupling glutaraldehyde (GA) and cellulose reaction. Subsequently, a metal oxide is intentionally infiltrated into inner cellulosic through MPI technology to form a third form of crosslinking, accompanied by the ultra-thin metal oxide nano-layer onto the surface of regenerated cellulose fibers. Results showed that the triple-crosslinking strategy has increased the tensile stress of the fiber by 43.57 % to 287.03 MPa. In all, triple-crosslinking strategy provides a theoretical basis and technical approach for the reinforcement of weak fibers in waste cotton recycling, which is expected to accelerate the development of the waste textile recycling industry and promote of the added-value of regenerated products.

Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis.

BACKGROUND: It is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients. METHODS: Comprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia. RESULTS: A total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]µmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]µmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943). CONCLUSIONS: According to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

Follicular fluid exosomes inhibit expression of BTG2 and promote glucose uptake in granulosa cells by delivering miR-21-5p.

Glucose metabolism in granulosa cells (GCs) is essential for follicle development and oocyte maturation. Porcine follicular fluid exosomes promote the proliferation of porcine GCs and the synthesis of steroid hormones. However, their role in regulating glucose uptake in GCs is unclear. The objective of this study was to elucidate the effects of porcine follicular fluid exosomes on glucose uptake in porcine GCs and the intrinsic mechanisms involved. First, transcriptome sequencing revealed that glucose metabolism-related pathways were altered in GCs treated with follicular fluid exosomes. Next, in vitro culture experiments showed that glucose uptake was increased and the IRS1/AKT signaling pathway was activated in GCs after treatment with follicular fluid exosomes. Finally, miRNA sequencing of follicular fluid exosomes revealed that miR-21-5p was the most abundant miRNA. Subsequent investigations indicated that miR-21-5p promoted glucose uptake in GCs by targeting BTG2, which activated the IRS1/AKT signaling pathway. In conclusion, the findings of this study indicate that porcine follicular fluid exosomes promote glucose uptake in porcine GCs by delivering miR-21-5p, which inhibits the expression of BTG2, activating the IRS1/AKT signaling pathway.

TL1A promotes metastasis and EMT process of colorectal cancer.

Background: Metastasis is the major problem of colorectal cancer (CRC) and is correlated with the high mortality. Tumor necrosis factor-like cytokine 1A (TL1A) is a novel regulatory factor for inflammatory diseases. This work aimed to investigate the role of TL1A in CRC metastasis. Method: AOM/DSS-induced mouse model, xenograft tumor model and metastasis murine model were established to mimic the colitis-associated CRC and investigate CRC growth and metastasis in vivo. Colon tissues were assessed by hematoxylin/eosin (HE) staining and immunohistochemistry (IHC). CRC cell metastasis in vivo was observed using in vivo imaging system (IVIS). Cell viability and proliferation were examined using cell counting kit 8 (CCK-8) and EdU experiments. The expression of tumor growth factor ß (TGFß) and metastatic biomarkers were detected using western blotting experiment. The in vitro cell metastasis was measured by Transwell. Results: Knockdown of TL1A notably suppressed the generation of colonic tumors in azoxymethane/dextran sodium sulfate (AOM/DSS) model, suppressed in vivo CRC cell growth, as well as lung and liver metastasis. The inflammation response and inflammatory cell infiltration in tumor sites were decreased by TL1A depletion. The in vitro CRC cell growth and metastasis was also suppressed by shTL1A, along with altered expression of epithelial mesenchymal transition (EMT) biomarkers. TL1A depletion suppressed the level of the TGF-ß1 receptor (TßRI) and phosphorylation of Smad3 in CRC cells. Stimulation with TGF-ß recovered the CRC cell migration and invasion that suppressed by shTL1A. Conclusion: Our work implicated TL1A as a promoter of CRC generation and metastasis and defines TGF-ß/Smad3 signaling as mediator of TL1A-regualated CRC cell metastasis.

Exploring the impacts of senescence on implantation and early embryonic development using totipotent cell-derived blastoids.

INTRODUCTION: Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are limited. OBJECTIVES: Here, we aim to elucidate the impacts of senescence on implantation ability by employing blastoids to construct a novel research model. METHODS: We used a novel three-dimensional system with totipotent blastomere-like cells (TBLCs) to construct TBL-blastoids and established senescence-related embryo models derived from oxidative stress-induced TBLCs. RESULTS: Morphological and transcriptomic analyses revealed that TBL-blastoids exhibited characteristic blastocyst morphology, cell lineages, and a higher consistency in developmental rate. TBL-blastoids demonstrated the ability to develop into postimplantation structures in vitro and successfully implanted into mouse uteri, inducing decidualization and forming embryonic tissues. Importantly, senescence impaired the implantation potential of TBL-blastoids, effectively mimicking the impaired implantation ability and reduced pregnancy rates associated with advanced age. Furthermore, analysis of differentially expressed genes (DEGs) in human homologous deciduae revealed enrichment in multiple fertility-related diseases and other complications of pregnancy. The genes implicated in these diseases and the common DEGs identified in the lineage-like cells of the two types of TBL-blastoids and deciduae may represent potential targets for addressing impaired implantation potential. CONCLUSION: These results unveiled that TBL blastoids are an improved model for investigating implantation and early postimplantation, offering valuable insights into pregnancy-related disorders in women with advanced age and potential targets for therapeutic interventions.

lnc RNA LOC102163816 Promotes Proliferation of Porcine Follicular Granulosa Cells Via miR-455-3p/PTK2B/PI3K/AKT Pathway.

The proliferation and differentiation of granulosa cells (GCs) is a crucial process in follicular development. However, the molecular regulatory mechanism of follicular proliferation and differentiation of GCs needs further research. Studies have reported that follicular fluid exosomes are involved in regulation of proliferation of GCs, but the specific mechanism is unclear. This study demonstrated that LOC102163816 is upregulated in porcine GCs treated with follicular fluid exosomes. Further study defined LOC102163816 to be a novel long noncoding RNA that is highly homologous to human metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and enriched in porcine follicular fluid exosomes. We have speculated that LOC102163816 might have a cell-proliferative effect similar to that of MALAT1. We found that overexpression of LOC102163816 promoted transition from the G1 phase to the S phase of the cell cycle, thereby promoting proliferation of GCs. To explore the specific mechanism underlying this promotion of proliferation, miRNA sequencing was performed after overexpression of LOC102163816. Our results showed that LOC102163816 sponged miR-455-3p, promoting expression of protein tyrosine kinase 2 beta (PTK2B), thereby activating the PI3K/AKT signaling pathway to regulate proliferation of porcine follicular GCs. These findings provide useful insights into follicular development.

Protocol for the Generation of Human EPS-Blastoids Using a Three-Dimensional Two-Step Induction System.

Stem cell-derived embryos in vitro allow the exploration of the very early stages of human embryogenesis in vitro and are thus promising for widespread applications in developmental biology, related developmental disease modeling, and drug discovery. Several cell resources have been utilized, with different efficiencies and methods for generating human blastoids, a structure similar to natural blastocysts. Human EPS cells were reported to contribute to the embryonic and extraembryonic lineages and therefore can be a practical and efficient cell resource for constructing human blastoids. Here, we developed a three-dimensional, two-step induction system for generating human blastoids using human EPS cells. According to morphological and transcriptomic analysis, EPS-blastoids recapitulate the key developmental processes and cell lineages of human blastocysts. Moreover, in vitro extended culture for 8 and 10 days of EPS-blastoids can result in postimplantation embryonic structures. In this chapter, we describe a protocol that covers the generation, maintenance, and developmental phenocopying of human EPS blastoids.

Salidroside promotes healthy longevity by interfering with HSP90 activity.

Aging is a risk factor for human health and quality of life. Screening and development of novel supplements and medications to combat aging and delay the incidence of age-related diseases are of great significance. In this study, salidroside (SA), a primary natural small molecule from Rhodiola rosea, was investigated regarding its effects on life and healthspan and the underlying molecular mechanism(s) of anti-aging and antioxidation. Our results showed that SA effectively prolonged lifespan and exhibited anti-aging and antioxidative properties. Computer-assisted methods, label-free interaction analysis, and in vitro assays showed that SA directly bound heat shock protein 90 (HSP90). Furthermore, SA significantly inhibited the ATPase activity of HSP90, affecting the interaction between HSP90 and its interacting proteins and the expression of downstream genes to regulate lifespan and the oxidative stress response. Our findings provided new insights into the pharmacological properties of SA across multiple species and its potential as an anti-aging drug.

Model-based analysis of the incidence trends and transmission dynamics of COVID-19 associated with the Omicron variant in representative cities in China.

BACKGROUND: In 2022, Omicron outbreaks occurred at multiple sites in China. It is of great importance to track the incidence trends and transmission dynamics of coronavirus disease 2019 (COVID-19) to guide further interventions. METHODS: Given the population size, economic level and transport level similarities, two groups of outbreaks (Shanghai vs. Chengdu and Sanya vs. Beihai) were selected for analysis. We developed the SEAIQRD, ARIMA, and LSTM models to seek optimal modeling techniques for waves associated with the Omicron variant regarding data predictive performance and mechanism transmission dynamics, respectively. In addition, we quantitatively modeled the impacts of different combinations of more stringent interventions on the course of the epidemic through scenario analyses. RESULTS: The best-performing LSTM model showed better prediction accuracy than the best-performing SEAIQRD and ARIMA models in most cases studied. The SEAIQRD model had an absolute advantage in exploring the transmission dynamics of the outbreaks. Regardless of the time to inflection point or the time to Rt curve below 1.0, Shanghai was later than Chengdu (day 46 vs. day 12/day 54 vs. day 14), and Sanya was later than Beihai (day 16 vs. day 12/day 20 vs. day 16). Regardless of the number of peak cases or the cumulative number of infections, Shanghai was higher than Chengdu (34,350 vs. 188/623,870 vs. 2,181), and Sanya was higher than Beihai (1,105 vs. 203/16,289 vs. 3,184). Scenario analyses suggested that upgrading control level in advance, while increasing the index decline rate and quarantine rate, were of great significance for shortening the time to peak and Rt below 1.0, as well as reducing the number of peak cases and final affected population. CONCLUSIONS: The LSTM model has great potential for predicting the prevalence of Omicron outbreaks, whereas the SEAIQRD model is highly effective in revealing their internal transmission mechanisms. We recommended the use of joint interventions to contain the spread of the virus.