The gut microbiota contributes to methamphetamine-induced reproductive toxicity in male mice.

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.

Stepwise Toward Pure Blue Organic Light-Emitting Diodes by Synergetically Locking and Shielding Carbonyl/Nitrogen-Based MR-TADF Emitters.

Deep-blue multi-resonance (MR) emitters with stable and narrow full-width-at-half-maximum (FWHM) are of great importance for widening the color gamut of organic light-emitting diodes (OLEDs). However, most planar MR emitters are vulnerable to intermolecular interactions from both the host and guest, causing spectral broadening and exciton quenching in thin films. Their emission in the solid state is environmentally sensitive, and the color purity is often inferior to that in solutions. Herein, a molecular design strategy is presented that simultaneously narrows the FWHM and suppresses intermolecular interactions by combining intramolecular locking and peripheral shielding within a carbonyl/nitrogen-based MR core. Intramolecularly locking carbonyl/nitrogen-based bears narrower emission of 2,10-dimethyl-12,12-diphenyl-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione in solution and further with peripheral-shielding groups, deep-blue emitter (12,12-diphenyl-2,10-bis(9-phenyl-9H-fluoren-9-yl)-4H-benzo[9,1]quinolizino[3,4,5,6,7-defg]acridine-4,8(12H)-dione, DPQAO-F) exhibits ultra-pure emission with narrow FWHM (c.a., 24 nm) with minimal variations (∆FWHM ≤ 3 nm) from solution to thin films over a wide doping range. An OLED based on DPQAO-F presents a maximum external quantum efficiency (EQEmax) of 19.9% and color index of (0.134, 0.118). Furthermore, the hyper-device of DPQAO-F exhibits a record-high EQEmax of 32.7% in the deep-blue region, representing the first example of carbonyl/nitrogen-based OLED that can concurrently achieve narrow bandwidth in the deep-blue region and a high electroluminescent efficiency surpassing 30%.

A nomogram to predict cognitive function impairment in patients with chronic kidney disease: A national cross-sectional survey.

Background: Cognitive function impairment (CFI) is common in patients with chronic kidney disease (CKD) and significantly impacts treatment adherence and quality of life. This study aims to create a simplified nomogram for early CFI risk detection. Methods: Data were obtained from the National Health and Nutrition Examination Survey cycles spanning from 1999 to 2002 and again from 2011 to 2014. Stepwise logistic regression was used to select variables and construct a CFI risk prediction model. Furthermore, C-statistic and Brier Score (BS) assessed model performance. Additionally, Kaplan-Meier survival curves were utilised to assess risk group-death prognosis relationships. Results: Of the 545 participants in the CKD model development cohort, a total of 146 (26.8 %) had CFI. The final model included the variables of age, race, education, annual family income, body mass index, estimated glomerular filtration rate, serum albumin and uric acid. The model had a C-statistic of 0.808 (95 % confidence interval (CI): 0.769-0.847) and a BS of 0.149. Furthermore, the 5-fold cross-validation internal C-statistic was 0.764 (interquartile range: 0.763-0.807) and BS was 0.154. Upon external validation, the model's C-statistic decreased to 0.752 (95 % CI: 0.654-0.850) and its BS increased to 0.182. The Kaplan-Meier survival curves demonstrated that intermediate-to-high-risk participants had shorter overall survival time than low-risk participants (log-rank test: p = 0.00042). Conclusions: This study established an effective nomogram for predicting CFI in patients with CKD, which can be used for the early detection of CFI and guide the treatment of patients with CKD.

Single-Atom Iron Doped Carbon Dots with Highly Efficient Electrochemiluminescence for Ultrasensitive Detection of MicroRNAs.

Herein, single-atom iron doped carbon dots (SA Fe-CDs) were successfully prepared as novel electrochemiluminescence (ECL) emitters with high ECL efficiency, and a biosensor was constructed to ultrasensitively detect microRNA-222 (miRNA-222). Importantly, compared with the conventional without single-atom doped CDs with low ECL efficiency, SA Fe-CDs exhibited strong ECL efficiency, in which single-atom iron as an advanced coreactant accelerator could significantly enhance the generation of reactive oxygen species (ROS) from the coreactant S2O82- for improving the ECL efficiency. Moreover, a neoteric amplification strategy combining the improved strand displacement amplification with Nt.BbvCI enzyme-induced target amplification (ISDA-EITA) could produce 4 output DNAs in every cycle, which greatly improved the amplification efficiency. Thus, a useful ECL biosensor was built with a detection limit of 16.60 aM in the range of 100 aM to 1 nM for detecting traces of miRNA-222. In addition, miRNA-222 in cancer cell lysate (MHCC-97L) was successfully detected by using the ECL biosensor. Therefore, this strategy provides highly efficient single-atom doped ECL emitters for the construction of sensitive ECL biosensing platforms in the biological field and clinical diagnosis.

Meta-analysis identifying gut microbial biomarkers of Qinghai-Tibet Plateau populations and the functionality of microbiota-derived butyrate in high-altitude adaptation.

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.

Exploring a Hirudin variant from nonhematophagous leeches: Unraveling full-length sequence, alternative splicing, function, and potential as a novel anticoagulant polypeptide.

ETHNOPHARMACOLOGICAL RELEVANCE: Leeches exhibit robust anticoagulant activity, making them useful for treating cardiovascular diseases in traditional Chinese medicine. Whitmania pigra, the primary source species of leech-derived medicinal compounds in China, has been demonstrated to possess formidable anticoagulant properties. Hirudin-like peptides, recognized as potent thrombin inhibitors, are prevalent in hematophagous leeches. Considering that W. pigra is a nonhematophagic leech, the following question arises: does a hirudin variant exist in this species? AIM OF THE STUDY: In this study we identified the hirudin-encoding gene (WP_HV1) in the W. pigra genome. The goal of this study was to assess its anticoagulant activity and analyze the related mechanisms. MATERIALS AND METHODS: In this study, a hirudin-encoding gene, WP_HV1, was identified from the W. pigra genome, and its accurate coding sequence (CDS) was validated through cloning from cDNA extracted from fresh W. pigra specimens. The structure of WP_HV1 and the amino acids associated with its anticoagulant activity were determined by sequence and structural analysis and prediction of its binding energy to thrombin. E. coli was used for the expression of WP_HV1 and recombinant proteins with various structures and mutants. The anticoagulant activity of the synthesized recombinant proteins was then confirmed using thrombin time (TT). RESULTS: Validation of the WP_HV1 gene was accomplished, and three alternative splices were discovered. The TT of the blank sample exceeded that of the recombinant WP_HV1 sample by 1.74 times (0.05 mg/ml), indicating positive anticoagulant activity. The anticoagulant activity of WP_HV1 was found to be associated with its C-terminal tyrosine, along with the presence of 9 acidic amino acids on both the left and right sides. A significant reduction in the corresponding TT was observed for the mutated amino acids compared to those of the wild type, with decreases of 4.8, 6.6, and 3.9 s, respectively. In addition, the anticoagulant activity of WP_HV1 was enhanced and prolonged for 2.7 s when the lysine-67 residue was mutated to tryptophan. CONCLUSION: Only one hirudin-encoding variant was identified in W. pigra. The active amino acids associated with anticoagulation in WP_HV1 were resolved and validated, revealing a novel source for screening and developing new anticoagulant drugs.

Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT/mTOR and MAPK Signaling Pathways.

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.

Leucine zipper as a bridge for transaminase self-assembly: A fusion enzyme for efficient chiral conversion of d-phenylglycine.

Amino acid transferase is a family of enzymes used to catalyze and separate chiral amino acids. However, due to the low efficiency, by-products and reverse reactions occur in cascade reactions. Therefore, in the research, phenylglycine aminotransferase and aspartate aminotransferase were self-assembled in vitro by leucine zipper. The self-assembled enzyme system with d-phenylglycine and α-ketoglutarate as substrates were used for the chiral transformation reaction. By studying the enzyme combination, kinetic reaction stability and catalytic efficiency, it was found that the self-assembled enzyme showed improved stability and better affinity to the substrate than the control and achieved only ee value of 17.86% for the control at the substrate ratio was 1:2. In contrast, the self-assembled enzyme basically catalyzed the complete conversion of d-Phg to l-Phg, with the ee value as 99%. These results demonstrated the feasibility of the leucine zipper and the conversion of d-phenylglycine to the l-type by fusion enzyme.

Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs.

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

Cost-effectiveness and cost-utility of a digital technology-driven hierarchical healthcare screening pattern in China.

Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.

Mechanically treated Mn2O3 triggers peracetic acid activation for superior non-radical oxidation of micropollutants: Identification of reactive complexes.

This study used a simple mechanical ball milling strategy to significantly improve the ability of Mn2O3 to activate peracetic acid (PAA) for sustainable and efficient degradation of organic micropollutant (like bisphenol A, BPA). BPA was successfully removed and detoxified via PAA activation by the bm-Mn2O3 within 30 min under neutral environment, with the BPA degradation kinetic rate improved by 3.4 times. Satisfactory BPA removal efficiency can still be achieved over a wide pH range, in actual water and after reuse of bm-Mn2O3 for four cycles. The change in hydrophilicity of Mn2O3 after ball milling evidently elevated the affinity of Mn2O3 for binding to PAA, while the reduction in particle size exposed more active sites contributing partially to catalytic oxidation. Further analysis revealed that BPA oxidation in the ball mill-treated Mn2O3 (bm-Mn2O3)/PAA process mainly depends on the bm-Mn2O3-PAA complex (i.e., Mn(III)-OO(O)CCH3) mediated non-radical pathway rather than R-O• and Mn(IV). Especially, the existence of the Mn(III)-PAA complex was definitely verified by in situ Raman spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). Simultaneously, density functional theory calculations determined that PAA adsorbs readily on manganese sites thereby favoring the formation of Mn(III)-OO(O)CCH3 complexes. This study advances an in-depth understanding of the underlying mechanisms involved in the manganese oxide-catalyzed activation of PAA for superior non-radical oxidation of micropollutants.

In Situ Growth 3D GDY-NCNTs Nanocomposites for High-Performance Supercapacitors.

New binary carbon composites (GDY-NCNTs and GDY-CNTs) with a three-dimensional porous structure, which are synthesized by an in situ growth method, are adopted in this article. The GDY-NCNTs composites exhibit excellent specific capacitance performance (679 F g-1, 2 mV s-1, 139% increase compared to GDY-CNTs) and good cycling stability (with a capacity retention rate of up to 116% after 10000 cycles). The three-dimensional porous structure not only promotes ion transfer and increases the effective specific surface area to improve its specific capacitance performance but also adapts to the volume expansion and contraction during the charging and discharging process to improve its cycling stability. The presence of nitrogen doping in the carbon nanotubes of GDY-NCNTs increases the surface defects of the composites, provides more electrochemical points, and improves the surface wettability of the composites, further improving the electrochemical performance of the composites.

Association of cognitive impairment with the interaction between chronic kidney disease and depression: findings from NHANES 2011-2014.

BACKGROUND: Cognitive impairment (CoI), chronic kidney disease (CKD), and depression are prevalent among older adults and are interrelated, imposing a significant disease burden. This study evaluates the association of CKD and depression with CoI and explores their potential interactions. METHOD: Data for this study were sourced from the 2011-2014 National Health and Nutritional Examination Survey (NHANES). Multiple binary logistic regression models assessed the relationship between CKD, depression, and CoI while controlling for confounders. The interactions were measured using the relative excess risk of interaction (RERI), the attributable proportion of interaction (AP), and the synergy index (S). RESULTS: A total of 2,666 participants (weighted n = 49,251,515) were included in the study, of which 700 (16.00%) had CoI. After adjusting for confounding factors, the risk of CoI was higher in patients with CKD compared to non-CKD participants (odds ratio [OR] = 1.49, 95% confidence interval [CI]:1.12-1.99). The risk of CoI was significantly increased in patients with depression compared to those without (OR = 2.29, 95% CI: 1.73-3.03). Furthermore, there was a significant additive interaction between CKD and depression in terms of the increased risk of CoI (adjusted RERI = 2.01, [95% CI: 0.31-3.71], adjusted AP = 0.50 [95% CI: 0.25-0.75], adjusted S = 2.97 [95% CI: 1.27-6.92]). CONCLUSION: CKD and depression synergistically affect CoI, particularly when moderate-to-severe depression co-occurs with CKD. Clinicians should be mindful of the combined impact on patients with CoI. Further research is needed to elucidate the underlying mechanisms and assess the effects specific to different CKD stages.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

Dual roles of dopaminergic pathways in olfactory learning and memory in the oriental fruit fly, Bactrocera dorsalis.

Dopamine (DA) is a key regulator of associative learning and memory in both vertebrates and invertebrates, and it is widely believed that DA plays a key role in aversive conditioning in invertebrates. However, the idea that DA is involved only in aversive conditioning has been challenged in recent studies on the fruit fly (Drosophila melanogaster), ants and crabs, suggesting diverse functions of DA modulation on associative plasticity. Here, we present the results of DA modulation in aversive olfactory conditioning with DEET punishment and appetitive olfactory conditioning with sucrose reward in the oriental fruit fly, Bactrocera dorsalis. Injection of DA receptor antagonist fluphenazine or chlorpromazine into these flies led to impaired aversive learning, but had no effect on the appetitive learning. DA receptor antagonists impaired both aversive and appetitive long-term memory retention. Interestingly, the impairment on appetitive memory was rescued not only by DA but also by octopamine (OA). Blocking the OA receptors also impaired the appetitive memory retention, but this impairment could only be rescued by OA, not by DA. Thus, we conclude that in B. dorsalis, OA and DA pathways mediate independently the appetitive and aversive learning, respectively. These two pathways, however, are organized in series in mediating appetitive memory retrieval with DA pathway being at upstream. Thus, OA and DA play dual roles in associative learning and memory retrieval, but their pathways are organized differently in these two cognitive processes - parallel organization for learning acquisition and serial organization for memory retrieval.

Tricholoma matsutake polysaccharides suppress excessive melanogenesis via JNK-mediated pathway: Investigation in 8- methoxypsoralen induced B16-F10 melanoma cells and clinical study.

Skin hyperpigmentation is a worldwide condition associated with augmented melanogenesis. However, conventional therapies often entail various adverse effects. Here, we explore the safety range and depigmentary effects of polysaccharides extract of Tricholoma matsutake (PETM) in an in vitro model and further evaluated its efficacy at the clinical level. An induced-melanogenesis model was established by treating B16-F10 melanoma cells with 8-methoxypsoralen (8-MOP). Effects of PETM on cell viability and melanin content were examined and compared to a commonly used depigmentary agent, α-arbutin. Expressions of key melanogenic factors and upstream signaling pathway were analysed by quantitative PCR and western blot. Moreover, a placebo-controlled clinical study involving Chinese females with skin hyperpigmentation was conducted to measure the efficacy of PETM on improving facial pigmented spots, melanin index, and individual typology angle (ITA°). Results demonstrated that PETM (up to 0.5 mg/mL) had little effect on the viability and motility of B16-F10 cells. Notably, it significantly suppressed the melanin content and expressions of key melanogenic factors induced by 8-MOP in B16-F10 melanoma cells. Western blotting results revealed that PETM inhibited melanogenesis by inactivating c-Jun N-terminal kinase (JNK), and this inhibitory role could be rescued by JNK agonist treatment. Clinical findings showed that PETM treatment resulted in a significant reduction of facial hyperpigmented spot, decreased melanin index, and improved ITA° value compared to the placebo-control group. In conclusion, these in vitro and clinical evidence demonstrated the safety and depigmentary efficacy of PETM, a novel polysaccharide agent. The distinct mechanism of action of PETM on melanogenic signaling pathway positions it as a promising agent for developing alternative therapies.

Tenecteplase versus alteplase for acute ischemic stroke: a systematic review and meta-analysis of randomized and non-randomized studies.

OBJECTIVE: Alteplase is the current standard of care for acute ischemic stroke. Tenecteplase is a newer fibrinolytic agent with preferable administration and lower costs; however, its comparative effectiveness to alteplase remains uncertain. We set out to perform a systematic review and meta-analysis to establish the benefits and harms of tenecteplase versus alteplase for acute ischemic stroke. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to April 2023 for randomized and non-randomized studies that compared tenecteplase versus alteplase for acute ischemic stroke. Paired reviewers independently assessed risk of bias and extracted data. We performed both conventional meta-analyses and Bayesian network meta-analyses (NMA) with random-effects models and used the GRADE approach to evaluate the certainty of evidence. Our primary efficacy outcome was excellent functional outcome at 3 months, defined as a score of 0-1 on the modified Rankin Scale. Our primary safety outcomes were symptomatic intracranial hemorrhage and all-cause mortality. RESULTS: Thirty-six studies were eligible for review, including 12 randomized (n = 5533) and 24 non-randomized studies (n = 44,956). Moderate certainty evidence showed that there was no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months (odds ratio [OR], 1.10; 95% CI 0.98-1.23; risk difference [RD] 2.4%, 95% CI - 0.5 to 5.2), while moderate certainty evidence from NMA suggested that 0.25 mg/kg tenecteplase significantly improved excellent functional outcome at 3 months (OR, 1.16; 95% credible interval 1.02-1.32). Moderate certainty evidence showed that, compared to alteplase, tenecteplase may make little to no difference in the prevalence of symptomatic intracranial hemorrhage (OR, 1.12; 95% CI 0.79-1.59; RD 0.3%, 95% CI - 0.5 to 1.4), and probably reduces all-cause mortality (adjusted odds ratio [aOR], 0.44; 95% CI 0.30-0.64; RD - 4.6%; 95% CI - 5.8 to - 2.9). CONCLUSIONS: Moderate certainty evidence suggested that there was little to no difference between tenecteplase and alteplase in increasing the proportion of patients achieving excellent functional outcome at 3 months and the risk of symptomatic intracranial hemorrhage, while compared to alteplase, tenecteplase probably reduce all-cause mortality. Administration of 0.25 mg/kg tenecteplase after acute ischemic stroke is suggestive of increasing the proportion of patients that achieve excellent functional outcome at 3 months.

OsWRKY78 regulates panicle exsertion via gibberellin signaling pathway in rice.

Panicle exsertion is one of the crucial agronomic traits in rice (Oryza sativa). Shortening of panicle exsertion often leads to panicle enclosure and severely reduces seed production. Gibberellin (GA) plays important roles in regulating panicle exsertion. However, the underlying mechanism and the relative regulatory network remain elusive. Here, we characterized the oswrky78 mutant showing severe panicle enclosure, and found that the defect of oswrky78 is caused by decreased bioactive GA contents. Biochemical analysis demonstrates that OsWRKY78 can directly activate GA biosynthesis and indirectly suppress GA metabolism. Moreover, we found OsWRKY78 can interact with and be phosphorylated by mitogen-activated protein kinase (MAPK) kinase OsMAPK6, and this phosphorylation can enhance OsWRKY78 stability and is necessary for its biological function. Taken together, these results not only reveal the critical function of OsWRKY78, but also reveal its mechanism via mediating crosstalk between MAPK and the GA signaling pathway in regulating panicle exsertion.

Abnormal energy metabolism, oxidative stress, and polyunsaturated fatty acid metabolism in depressed adolescents associated with childhood maltreatment: A targeted metabolite analysis.

The purpose of this study was to explore the metabolomic differences between Major depressive disorder (MDD) and healthy individuals among adolescents and the association between childhood maltreatment (CM) and differentially abundant metabolites. The exploratory study included 40 first-episode drug-naïve adolescents with MDD and 20 healthy volunteers. We used the Beck Depression Inventory (BDI-13) to assess the severity of depression and the Childhood Trauma Questionnaire (CTQ) to assess the presence of childhood maltreatment. The plasma samples from all participants were collected for targeted metabolomics analysis using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS) methods. Spearman correlation was applied to analyse the correlations between clinical variables and metabolites. We found 11 increased metabolites and 37 decreased metabolites that differed between adolescents with MDD and healthy individuals. Pathway enrichment analysis of differentially abundant metabolites showed abnormalities in energy metabolism and oxidative stress in MDD. Importantly, we found that creatine, valine, isoleucine, glutamic acid and pyroglutamic acid were negatively correlated with the BDI-13, while isocitric acid, fatty acid and acylcarnitine were negatively associated with CTQ, and 4-hydroxyproline was positively related to CTQ in adolescents with MDD. These studies provide new ideas for the pathogenesis and potential treatment of adolescents with MDD.

Temporal interference stimulation targets deep primate brain.

Temporal interference (TI) stimulation, a novel non-invasive stimulation strategy, has recently been shown to modulate neural activity in deep brain regions of living mice. Yet, it is uncertain if this method is applicable to larger brains and whether the electric field produced under traditional safety currents can penetrate deep regions as observed in mice. Despite recent model-based simulation studies offering positive evidence at both macro- and micro-scale levels, the absence of electrophysiological data from actual brains hinders comprehensive understanding and potential application of TI. This study aims to directly measure the spatiotemporal properties of the interfered electric field in the rhesus monkey brain and to validate the effects of TI on the human brain. Two monkeys were involved in the measurement, with implantation of several stereo-electroencephalography (SEEG) depth electrodes. TI stimulation was applied to anesthetized monkeys using two pairs of surface electrodes at differing stimulation parameters. Model-based simulations were also conducted and subsequently compared with actual recordings. Additionally, TI stimulation was administered to patients with motor disorders to validate its effects on motor symptoms. Through the integration of computational electric field simulation with empirical measurements, it was determined that the temporally interfering electric fields in the deep central regions are capable of attaining a magnitude sufficient to induce a subthreshold modulation effect on neural signals. Additionally, an improvement in movement disorders was observed as a result of TI stimulation. This study is the first to systematically measure the TI electric field in living non-human primates, offering empirical evidence that TI holds promise as a more focal and precise method for modulating neural activities in deep regions of a large brain. This advancement paves the way for future applications of TI in treating neuropsychiatric disorders.