CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Light recovery after maize harvesting promotes soybean flowering in a maize-soybean relay strip intercropping system.

Moving from sole cropping to intercropping is a transformative change in agriculture, contributing to yield. Soybeans adapt to light conditions in intercropping by adjusting the onset of reproduction and the inflorescence architecture to optimize reproductive success. Maize-soybean strip intercropping (MS), maize-soybean relay strip intercropping (IS), and sole soybean (SS) systems are typical soybean planting systems with significant differences in light environments during growth periods. To elucidate the effect of changes in the light environment on soybean flowering processes and provide a theoretical basis for selecting suitable varieties in various planting systems to improve yields, field experiments combining planting systems (IS, MS, and SS) and soybean varieties (GQ8, GX7, ND25, and NN996) were conducted in 2021 and 2022. Results showed that growth recovery in the IS resulted in a balance in the expression of TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) in the meristematic tissues of soybeans, which promoted the formation of new branches or flowers. IS prolonged the flowering time (2-7 days) and increased the number of forming flowers compared with SS (93.0 and 169%) and MS (67.3 and 103.3%) at the later soybean flowering stage. The higher carbon and nitrogen content in the middle and bottom canopies of soybean contributed to decreased flower abscission by 26.7 and 30.2%, respectively, compared with SS. Canopy light environment recovery promoted branch and flower formation and transformation of flowers into pods with lower flower-pod abscission, which contributed to elevating soybean yields in late-maturing and multibranching varieties (ND25) in IS.

VASN promotes colorectal cancer progression by activating the YAP/TAZ and AKT signaling pathways via YAP.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. Vasorin (VASN) has been reported to be critical in tumor development and angiogenesis. However, VASN has not been reported in CRC, and its role is unclear. In this study, VASN expression is upregulated in CRC compared with the normal tissues, and VASN expression positively correlates with N stage and poor overall survival by analysis of different datasets and 32 CRC clinicopathologic samples. Overexpression of VASN significantly promotes CRC cell progression, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while knockdown of VASN inhibits CRC progression. We found that VASN was associated with the YAP/TAZ and PI3K/AKT pathways by gene set enrichment analysis (GSEA) and gene ontology (GO) analysis. Notably, western blotting, immunofluorescence staining and co-immunofluorescence (co-IP) confirmed that VASN could interact with YAP and activate the YAP/TAZ and PTEN/PI3K/AKT pathways, and knockdown of YAP reversed this effect. Importantly, our findings indicate that VASN interacts with YAP to inhibit YAP phosphorylation and stimulates CRC proliferation, migration, and invasion through activation of the YAP/TAZ-TEAD target gene CTGF and PTEN/PI3K/AKT pathways. Our results also show that knockdown of YAP reverses the cellular phenotype induced by increased VASN. In conclusion, our study reveals that VASN acts as an oncogene to stimulate tumor progression in CRC, providing new insights into the molecular mechanisms of CRC development and representing a possible novel biomarker for CRC.

Abscisic acid facilitates phosphate acquisition through the transcription factor ABA INSENSITIVE5 in Arabidopsis.

Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in the plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter roots and less Pi content than wild-type plants under LP conditions. Moreover, a mutant of ABI5, which encodes a central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP conditions. ABI5 facilitated Pi acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpression of PHT1;1 completely rescued its Pi content under LP conditions. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in the Arabidopsis response to phosphate deficiency.

PoDPBT, a BAHD acyltransferase, catalyses the benzoylation in paeoniflorin biosynthesis in Paeonia ostii.

PoDPBT, an O-benzoyltransferase belonging to the BAHD family, can catalyze the benzoylation of 8-debenzoylpaeoniflorin to paeoniflorin. PoDPBT is the first enzyme demonstrated to be involved in the modification stage of paeoniflorin biosynthesis. DFGGG, a new DFGWG-like motif, was revealed in the BAHD family. The transcriptome database provides a resource for further investigation of other enzyme genes involved in paeoniflorin biosynthesis.

Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy.

BACKGROUND: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP. METHODS: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls. 16S rRNA sequencing and nontargeting metabolomics were adapted to explore the gut microbiome and fecal metabolites. RESULTS: An increase in richness and a dramatic deviation in composition were found in the gut microbiome in ICP. Decreased Firmicutes and Bacteroidetes abundances and increased Proteobacteria abundances were found in women with severe but not mild ICP compared to healthy pregnant women. Escherichia-Shigella and Lachnoclostridium abundances increased, whereas Ruminococcaceae abundance decreased in ICP group, especially in severe ICP group. The fecal metabolite composition and diversity presented typical variation in severe ICP. A significant increase in bile acid, formate and succinate levels and a decrease in butyrate and hypoxanthine levels were found in women with severe ICP. The MIMOSA model indicated that genera Ruminococcus gnavus group, Lachnospiraceae FCS020 group, and Lachnospiraceae NK4A136 group contributed significantly to the metabolism of hypoxanthine, which was significantly depleted in subjects with severe ICP. Genus Acinetobacter contributed significantly to formate metabolism, which was significantly enriched in subjects with severe ICP. CONCLUSIONS: Women with severe but not mild ICP harbored a unique gut microbiome and fecal metabolites compared to healthy controls. Based on these profiles, we hypothesized that the gut microbiome was involved in bile acid metabolism through metabolites, affecting ICP pathogenesis and development, especially severe ICP.

CycC1;1 negatively modulates ABA signaling by interacting with and inhibiting ABI5 during seed germination.

Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.

Comprehensive Analysis of 34 Edible Flowers by the Determination of Nutritional Composition and Antioxidant Capacity Planted in Yunnan Province China.

The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (·OH) scavenging and superoxide anion radical (·O2-) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.

Overexpression of PD-L1 causes germ cells to slough from mouse seminiferous tubules via the PD-L1/PD-L1 interaction.

Spermatogenesis is a cyclical process in which different generations of spermatids undergo a series of developmental steps at a fixed time and finally produce spermatids. Here, we report that overexpression of PD-L1 (B7 homolog1) in the testis causes sperm developmental disorders and infertility in male mice, with severe malformation and sloughing during spermatid development, characterized by disorganized and collapsed seminiferous epithelium structure. PD-L1 needs to be simultaneously expressed on Sertoli cells and spermatogonia to cause spermatogenesis failure. After that, we excluded the influence of factors such as the PD-L1 receptor and humoral regulation, confirming that PD-L1 has an intrinsic function to interact with PD-L1. Studies have shown that PD-L1 not only serves as a ligand but also plays a receptor-like role in signal transduction. PD-L1 interacts with PD-L1 to affect the adhesive function of germ cells, causing malformation and spermatid sloughing. Taken together, these results indicate that PD-L1 can interact with PD-L1 to cause germ cell detachment and male infertility.

PD-L1/PD-L1 signalling promotes colorectal cancer cell migration ability through RAS/MEK/ERK.

Programmed death ligand 1 (PD-L1) is widely known as an immune checkpoint, and immunotherapy through the inhibition of checkpoint molecules has become an important component in the successful treatment of tumours via programmed death 1 (PD-1)/PD-L1 signalling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) are elusive. We previously found that PD-L1 can bind to PD-L1 and cause cell detachment. However, the detailed molecular mechanisms of how PD-L1 binds to PD-L1 and how it transmits signals to the cell remain unclear. In this study, we disclosed that PD-L1 expression was dramatically upregulated in CRC compared to normal tissues. Ectopic expression of PD-L1 inhibits cell adhesive capacity and promotes cell migration in CRC cell lines, while silencing PD-L1 had the opposite effects and suppressed invasion and proliferation. Mechanistically, PD-L1 was found to promote epithelial-mesenchymal transition (EMT) through the ERK signalling molecule pathway and interacted with the 1-86 aa fragment of KRAS to transduce signals. Collectively, our study demonstrated the role of PD-L1 after binding to PD-L1 in CRC, thereby providing a new theoretical basis for further improving immunotherapy with anti-PD-L1 antibodies.

[Levo-tetrahydropalmatine promotes apoptosis of human hepatocellular carcinoma through switching energy metabolism phenotype via upregulation of mitochondrial reactive oxygen species].

Mitochondrion is an important organelle that maintains cellular homeostasis and plays a crucial role in determining cell fate. The present study investigated the effect of levo-tetrahydropalmatine(THP) on autophagic flux and energy metabolism phenotype of human hepatocellular carcinoma(HCC) SMMC-7721 and BEL-7402 cells. SMMC-7721 and BEL-7402 cells were treated with THP(100 µmol·L~(-1)) with or without N-acetyl-L-cysteine(NAC, 10 µmol·L~(-1)) for 24 h. The mitochondrial reactive oxygen species(mtROS) was detected by flow cytometry(FCM) with MitoSOX probe and fluorescence microscopy, respectively. Thereafter, autophagic flux was detected by FCM with CYTO-ID probe, and the protein levels of microtubule-associated protein 1 A/1 B-light chain 3-Ⅰ(LC3Ⅰ), LC3Ⅱ, and phosphorylated AMP-activated protein kinase(p-AMPK)/AMPK were measured by Western blot. Mitochondrial respiration was examined by Seahorse XFp assay and cell proliferation by a system. Annexin V-FITC and PI/RNase staining was employed to detect apoptosis of SMMC-7721 and BEL-7402 cells treated with THP and/or NAC. Subsequently, membrane potential was measured with MitoTracker Red CMXRos. Compared with the control group, THP promoted mtROS production and THP combined with NAC attenuated the autophagic flux increase induced by THP alone in SMMC-7721 and BEL-7402 cells. When cells were co-treated with THP and chloroquine(CQ, an autophagy inhibitor), THP further increased mtROS and apoptosis. In addition, THP significantly reduced mitochondrial respiration in terms of mitochondrial basal respiration, ATP production, and maximal respiration. Meanwhile, THP significantly reduced the proliferation index and mitochondrial membrane potential of HCC cells accompanied by the increased apoptosis. This study demonstrates that the up-regulation of mtROS by THP significantly promotes HCC cell autophagy(protective autophagy) and impairs mitochondrial respiration through reprogramming energy metabolism, ultimately inducing the mitochondria-mediated apoptosis of SMMC-7721 and BEL-7402 cells.

Engineering of Reversible NIR-II Redox-Responsive Fluorescent Probes for Imaging of Inflammation In Vivo.

The second near-infrared (NIR-II) fluorescent imaging shows great potential for deep tissue analysis at high resolution in living body owing to low background autofluorescence and photon scattering. However, reversible monitoring of redox homeostasis using NIR-II fluorescent imaging remains a challenge due to the lack of appropriate probes. In this study, a series of stable and multifunctional NIR-II dyes (NIR-II Cy3s) were constructed based on trimethine skeleton. Significantly, introducing the 1,4-diethyl-decahydroquinoxaline group to the NIR-II Cy3s not only effectively increased the wavelength, but also served as an effective response site for HClO, which can be restored by reactive sulfur species (RSS). Based on this, NIR-II Cy3s were used for reversible monitoring of HClO/RSS-mediated redox processes in the pathophysiology environment. Finally, NIR-II Cy3-988 was successfully utilized for assessment of the redox environments and drug treatment effects in acute inflammation model.

Maternal chronic hepatitis B virus infection and the risk of preterm birth: A retrospective cohort analysis in Chinese women.

The association between different clinical states of chronic HBV infection and preterm birth (PTB) is still controversial. A retrospective cohort study among 57,386 pregnant women was conducted to examine the impact of chronic HBsAg positive, both HBsAg and HBeAg positive, and chronic active hepatitis on pregnancy complications related to the overall PTB and its subtypes (spontaneous and iatrogenic). A total of 54,245 pregnancies were included in the final study cohort, among which 2,151(4.0%) pregnant women were HBsAg positive. The PTB rate was 6.0% (129/2151) for HBV-infected women while 4.5% (2319/52094) for those not. Compared with women not infected with HBV, multivariable-adjusted analyses showed HBV-infected women had a 33% higher risk of overall PTB (aRR 1.33 95%CI, 1.11-1.60), a 27% higher risk of spontaneous PTB (aRR 1.27, 95% CI, 1.02-1.57) and a 50% higher risk of iatrogenic PTB (aRR 1.50, 95%CI, 1.07-2.11). The PTB rate was 8.9% (35/395) for both HBsAg and HBeAg-positive women and 16.2% (22/136) for women with active chronic hepatitis. Multivariable-adjusted analyses showed women who were both HBsAg and HBeAg positive had a 47% higher risk of overall PTB (aRR 1.47, 95%CI, 1.04-2.09), a 2.03 times higher risk of spontaneous PTB (aRR 2.03, 95%CI, 1.38-2.99) and a 32% higher risk of iatrogenic PTB (aRR 1.32, 95%CI, 0.62-2.81), while women with chronic active hepatitis had a 3.84 times higher risk of overall PTB (aRR 3.84, 95%CI, 2.42-6.10), a 3.88 times higher risk of spontaneous PTB (aRR 3.88, 95%CI, 2.32-6.45) and a 3.01 times higher risk of iatrogenic PTB (aRR 3.01, 95%CI, 1.22-7.44). Different maternal clinical states of chronic HBV infection are independently associated with an increased risk of overall PTB and its subtypes (spontaneous and iatrogenic).

Design and synthesis of new indole containing biaryl derivatives as potent antiproliferative agents.

A new series of indole containing biaryl derivatives were designed and synthesized, and further biological evaluations of their antiproliferative activity against cancer cell lines (MGC-803 and TE-1 cells) were also conducted. Of these synthesized biaryls, compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) performed as the most potent antiproliferative agent that inhibited cell viability of MGC-803 cells with an IC50 value of 8.28 µM. In addition, investigation of mechanism exhibited that the compound 4-methyl-2-((5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)methyl)quinazoline (23) could inhibit the expression of c-Myc and glycolysis related proteins, decrease the ATP and lactate production, and further induce apoptosis by activating the AMP-activated protein kinase (AMPK) and p53 signaling pathways.

Direct bacteria analysis using laserspray ionization miniature mass spectrometry.

An atmospheric pressure laserspray ionization mass spectrometry (AP-LSI mini MS) has been developed and employed in the fast analysis of bacteria. Without using surfactants or any extracting methods, 21 foodborne bacteria from 12 genera were directly analyzed. Typical fingerprints of small molecules and lipids were detected and recognized in the mass spectra with high reproducibility. Furthermore, a supervised multivariate statistics method, orthogonal partial least squares (OPLS), was applied, and these bacteria could be differentiated at both genus and species levels. With improved performance in the future, AP-LSI mini MS could be a simple, effective, and fast approach for direct bacteria analysis on the field.

Mitochondrial ABC Transporter ATM3 Is Essential for Cytosolic Iron-Sulfur Cluster Assembly.

The mitochondrial ATP-binding cassette transporter ATM3 has been studied in Arabidopsis. Its function, however, is poorly understood in other model plant species. This study reports that the ATM3 is required for cytosolic iron-sulfur cluster assembly and is essential for meristem maintenance in rice (Oryza sativa). The loss of function of OsATM3 is lethal in rice at the four-leaf stage. In the osatm3 T-DNA insertion mutant, the fourth leaf fails to develop and the lateral roots are short. Cytosolic iron-sulfur protein activities were significantly reduced in both osatm3 and RNA interference transgenic lines. The expression profiles of many iron metabolism genes were altered in the osatm3 and RNA interference lines. Glutathione metabolism was impaired and reactive oxygen species, particularly superoxide, accumulated in osatm3 Promoter-ß-glucuronidase staining of the transgenic line indicated that OsATM3 is highly expressed in lateral root primordia, root tip meristem zones, and shoot apical meristem regions. The average cell size was significantly greater in osatm3 than in the wild type. Massive cell death occurred in the osatm3 root tip meristem zone. Quantitative RT-PCR revealed transcriptional reprogramming of the genes in the osatm3 and RNAi lines involved in DNA repair and cell cycle arrest. Our results suggest that the mitochondrial ATM3 is essential for iron homeostasis in rice.

Soybean Fe-S cluster biosynthesis regulated by external iron or phosphate fluctuation.

KEY MESSAGE: Iron and phosphorus are essential for soybean nodulation. Our results suggested that the deficiency of Fe or P impairs nodulation by affecting the assembly of functional iron-sulfur cluster via different mechanisms. Iron (Fe) and phosphorus (P) are important mineral nutrients for soybean and are indispensable for nodulation. However, it remains elusive how the pathways of Fe metabolism respond to the fluctuation of external Fe or P. Iron is required for the iron-sulfur (Fe-S) cluster assembly in higher plant. Here, we investigated the expression pattern of Fe-S cluster biosynthesis genes in the nodulated soybean. Soybean genome encodes 42 putative Fe-S cluster biosynthesis genes, which were expressed differently in shoots and roots, suggesting of physiological relevance. Nodules initiated from roots of soybean after rhizobia inoculation. In comparison with that in shoots, iron concentration was three times higher in nodules. The Fe-S cluster biosynthesis genes were activated and several Fe-S protein activities were increased in nodules, indicating that a more effective Fe-S cluster biosynthesis is accompanied by nodulation. Fe-S cluster biosynthesis genes were massively repressed and some Fe-S protein activities were decreased in nodules by Fe deficiency, leading to tiny nodules. Notably, P deficiency induced a similar Fe-deficiency response in nodules, i.e, certain Fe-S enzyme activity loss and tiny nodules. However, distinct from Fe-deficient nodules, higher iron concentration was accumulated and the Fe-S cluster biosynthesis genes were not suppressed in the P-deficiency-treated nodules. Taken together, our results showed that both Fe deficiency and P deficiency impair nodulation, but they affect the assembly of Fe-S cluster maybe via different mechanisms. The data also suggested that Fe-S cluster biosynthesis likely links Fe metabolism and P metabolism in root and nodule cells of soybean.

Uchl1 and its associated proteins were involved in spermatocyte apoptosis in mouse experimental cryptorchidism.

Uchl1 was found to be involved in spermatocyte apoptosis. The aim of the present study was to test whether Uchl1 and its associated proteins Jab1 and p27(kip1) were involved in spermatogenic damages in response to heat-stress in cryptorchidism. Hematoxylin and eosin (HE) staining and DNA end labeling (TUNEL) were used to observe morphological and apoptotic characteristics of spermatogenic cells; Immunohistochemical analysis was used to detect changes of Uchl1 and its associated proteins Jab1 and p27(kip1) in response to heat-stress from cryptorchidism leading to spermatocyte losses; And protein affinity analysis (pull-down) and immunofluorescence co-localization were used to verify the relevance among the three proteins in spermatocytes. The results showed that, Jab1 and p27(kip1), in parallel to Uchl1, increased in spermatocytes of apoptotic appearances in response to heat-stress, but not in multinucleated giant cells; Jab1 bound to Uchl1 in testis protein extracts, and co-localized with Uchl1 and p27(kip1) specifically in spermatocytes with apoptotic appearances. These results suggest that the accumulation of Uchl1 protein is involved in the heat-stress-induced spermatocyte apoptosis through a new pathway related with Jab1 and p27(kip1), but not the formation of multinucleated giant cells.

Electro-acupuncture modulated miR-214 expression to prevent chondrocyte apoptosis and reduce pain by targeting BAX and TRPV4 in osteoarthritis rats.

Osteoarthritis (OA) is a highly prevalent joint disorder characterized by progressive degeneration of articular cartilage, subchondral bone remodeling, osteophyte formation, synovial inflammation, and meniscal damage. Although the etiology of OA is multifactorial, pro-inflammatory processes appear to play a key role in disease pathogenesis. Previous studies indicate that electroacupuncture (EA) exerts chondroprotective, anti-inflammatory, and analgesic effects in preclinical models of OA, but the mechanisms underlying these potential therapeutic benefits remain incompletely defined. This study aimed to investigate the effects of EA on OA development in a rat model, as well as to explore associated molecular mechanisms modulated by EA treatment. Forty rats were divided into OA, EA, antagomiR-214, and control groups. Following intra-articular injection of monosodium iodoacetate to induce OA, EA and antagomiR-214 groups received daily EA stimulation at acupoints around the knee joint for 21 days. Functional pain behaviors and chondrocyte apoptosis were assessed as outcome measures. The expression of microRNA-214 (miR-214) and its downstream targets involved in apoptosis and nociception, BAX and TRPV4, were examined. Results demonstrated that EA treatment upregulated miR-214 expression in OA knee cartilage. By suppressing pro-apoptotic BAX and pro-nociceptive TRPV4, this EA-induced miR-214 upregulation ameliorated articular pain and prevented chondrocyte apoptosis. These findings suggested that miR-214 plays a key role mediating EA's therapeutic effects in OA pathophysiology, and represents a promising OA treatment target for modulation by acupuncture.

Association between tobacco exposure and bladder cancer recurrence: A systematic review and meta-analysis.

BACKGROUND: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear. AIM: To determine whether smoking is linked to the recurrence and progression of bladder cancer. METHODS: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61). CONCLUSION: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer.