Overexpression of Larch SCL6 Inhibits Transitions from Vegetative Meristem to Inflorescence and Flower Meristem in Arabidopsis thaliana (L.) Heynh.

SCARECROW-LIKE6 (SCL6) plays a role in the formation and maintenance of the meristem. In Larix kaempferi (Lamb.) Carr., an important afforestation tree species in China, SCL6 (LaSCL6) has two alternative splicing variants-LaSCL6-var1 and LaSCL6-var2-which are regulated by microRNA171. However, their roles are still unclear. In this study, LaSCL6-var1 and LaSCL6-var2 were transformed into the Arabidopsis thaliana (L.) Heynh. genome, and the phenotypic characteristics of transgenic A. thaliana, including the germination percentage, root length, bolting time, flower and silique formation times, inflorescence axis length, and branch and silique numbers, were analyzed to reveal their functions. It was found that LaSCL6-var1 and LaSCL6-var2 overexpression shortened the root length by 41% and 31%, respectively, and increased the inflorescence axis length. Compared with the wild type, the bolting time in transgenic plants was delayed by approximately 2-3 days, the first flower and silique formation times were delayed by approximately 3-4 days, and the last flower and silique formation times were delayed by about 5 days. Overall, the life cycle in transgenic plants was prolonged by approximately 5 days. These results show that LaSCL6 overexpression inhibited the transitions from the vegetative meristem to inflorescence meristem and from the flower meristem to meristem arrest in A. thaliana, revealing the roles of LaSCL6-var1 and LaSCL6-var2 in the fate transition and maintenance of the meristem.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Cambium Reactivation Is Closely Related to the Cell-Cycle Gene Configuration in Larix kaempferi.

Dormancy release and reactivation in temperate trees are mainly controlled by temperature and are affected by age, but the underlying molecular mechanisms are still unclear. In this study, we explored the effects of low temperatures in winter and warm temperatures in spring on dormancy release and reactivation in Larix kaempferi. Further, we established the relationships between cell-cycle genes and cambium cell division. The results showed that chilling accelerated L. kaempferi bud break overall, and the longer the duration of chilling is, the shorter the bud break time is. After dormancy release, warm temperatures induced cell-cycle gene expression; when the configuration value of the cell-cycle genes reached 4.97, the cambium cells divided and L. kaempferi reactivated. This study helps to predict the impact of climate change on wood production and provides technical support for seedling cultivation in greenhouses.

[Identification of Protein-Coding Gene Markers in Breast Invasive Carcinoma Based on Machine Learning].

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer.

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men, respectively, worldwide. Although the antitumor activity of chalcones has been extensively studied, the molecular mechanisms of isoliquiritigenin analog 2', 4', 4-trihydroxychalcone (metochalcone; TEC) against carcinomas remain less well understood. In this study, we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner. TEC induced cell cycle arrest in the S-phase, cell migration inhibition in vitro, and reduced tumor growth in vivo. Moreover, transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways. TEC triggered the senescence-associated secretory phenotype (SASP) by repressing the JAK2/STAT3 axis. The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway, highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

Hypoxia-induced TREM1 promotes mesenchymal-like states of glioma stem cells via alternatively activating tumor-associated macrophages.

The mesenchymal subtype of glioblastoma (GBM) cells characterized by aggressive invasion and therapeutic resistance is thought to be dependent on cell-intrinsic alteration and extrinsic cellular crosstalk. Tumor-associated macrophages (TAMs) are pivotal in tumor progression, chemo-resistance, angiogenesis, and stemness maintenance. However, the impact of TAMs on the shifts in glioma stem cells (GSCs) states remains largely uncovered. Herein, we showed that the triggering receptor expressed on myeloid cells-1 (TREM1) preferentially expressed by M2-like TAMs and induced GSCs into mesenchymal-like states by modulating the secretion of TGFß2, which activated the TGFßR/SMAD2/3 signaling in GSCs. Furthermore, we demonstrated that TREM1 was transcriptionally regulated by HIF1a under the hypoxic environment and thus promoted an immunosuppressive type of TAMs via activating the TLR2/AKT/mTOR/c-MYC axis. Collectively, this study reveals that cellular communication between TAMs and GSCs through the TREM1-mediated TGFß2/TGFßR axis is involved in the mesenchymal-like transitions of GSCs. Our study provides valuable insights into the regulatory mechanisms between the tumor immune microenvironment and the malignant characteristics of GBM, which can lead to potential novel strategies targeting TAMs for tumor control.

[Arthroscopic suspension fixation with Endobutton in treatment of tibial insertion avulsion fractures of posterior cruciate ligament].

Objective: To investigate the effectiveness of arthroscopic suspension fixation with Endobutton in the treatment of tibial insertion avulsion fractures of posterior cruciate ligament (PCL). Methods: A retrospective analysis was conducted on the clinical data of 52 patients (52 knees) with tibial insertion avulsion fractures of PCL, who were treated by arthroscopic suspension fixation with Endobutton between June 2017 and October 2022. There were 29 males and 23 females, with an average age of 40.6 years (range, 19-66 years). There were 24 cases of traffic accident injuries, 17 cases of sports injuries, and 11 cases of fall injuries. The time from injury to operation ranged from 6 to 19 days (mean, 13.3 days). According to the Meyers-McKeever classification, there were 30 cases of type Ⅱ and 22 cases of type Ⅲ fractures. All patients exhibited positive posterior drawer test results. Preoperative knee joint function was assessed with Lysholm score (21.3±6.7), International Knee Documentation Committee (IKDC) score (20.7±5.8), and visual analogue scale (VAS) score (5.3±0.7); and knee joint range of motion was (41.73±3.17)°. Based on preoperative CT three-dimensional reconstruction measurements, the longitudinal diameter of the avulsed bone fragment ranged from 13 to 25 mm (mean, 18.1 mm). Operation time and occurrence of complications were recorded, and postoperative imaging was used to assess fracture healing. Knee joint function and pain severity were evaluated using knee joint range of motion, Lysholm score, IKDC score, and VAS score. Results: The operation time ranged from 46 to 81 minutes (mean, 56.2 minutes). All patients were followed up 12-28 months (mean, 20.1 months). The iatrogenic fractures of bone fragments occurred during operation in 4 cases; and knee effusion occurred in 2 cases and anterior knee pain in 1 case after operation. All incisions healed by first intention. Imaging evaluations at 3 months after operation showed the fracture healing and no internal fixation failure. All patients demonstrated good knee function and had returned to normal activities at 12 months after operation. At last follow-up, the knee joint range of motion was (133.44±4.17)°, Lysholm score 93.6±3.1, IKDC score 93.4±2.5, and VAS score 1.0±0.6, with significant differences compared to preoperative scores ( P<0.05). Conclusion: Arthroscopic suspension fixation with Endobutton in the treatment of tibial insertion avulsion fractures of PCL is simple to operate, and the knee joint function recovers well.

Generation of Ultrabrilliant Polarized Attosecond Electron Bunches via Dual-Wake Injection.

Laser wakefield acceleration is paving the way for the next generation of electron accelerators, for their own sake and as radiation sources. A controllable dual-wake injection scheme is put forward here to generate an ultrashort triplet electron bunch with high brightness and high polarization, employing a radially polarized laser as a driver. We find that the dual wakes can be driven by both transverse and longitudinal components of the laser field in the quasiblowout regime, sustaining the laser-modulated wakefield which facilitates the subcycle and transversely split injection of the triplet bunch. Polarization of the triplet bunch can be highly preserved due to the laser-assisted collective spin precession and the noncanceled transverse spins. In our three-dimensional particle-in-cell simulations, the triplet electron bunch, with duration about 500 as, six-dimensional brightness exceeding 10^{14} A/m^{2}/0.1% and polarization over 80%, can be generated using a few-terawatt laser. Such an electron bunch could play an essential role in many applications, such as ultrafast imaging, nuclear structure and high-energy physics studies, and the operation of coherent radiation sources.

[Effectiveness of combined anteversion angle technique in total hip arthroplasty for treatment of ankylosing spondylitis affecting hip joint].

Objective: To explore the effectiveness of the combined anteversion angle technique in total hip arthroplasty (THA) for treating ankylosing spondylitis (AS) affecting the hip joint. Methods: A retrospective analysis was conducted on the clinical data of 73 patients with AS affecting the hip joint who underwent THA between August 2018 and August 2021. According to whether the combined anteversion angle technique was used in THA, the patients were divided into study group (37 cases, combined anteversion angle technique was used in THA) and control group (36 cases, traditional THA). There was no significant difference in baseline data such as gender, age, body mass index, disease duration, preoperative Harris score, range of motion (ROM), acetabular anteversion angle, acetabular abduction angle, femoral anteversion angle, and combined anteversion angle between the two groups ( P>0.05). The operation time, hospital stay, and complications of the two groups were recorded and compared. The Harris score and hip ROM were compared between the two groups before operation, at 1, 3, 6, 12 months after operation, and at last follow-up. The acetabular component anteversion angle, femoral component anteversion angle, acetabular component abduction angle, and component combined anteversion angle were measured postoperatively. Results: The operation time in the study group was significantly shorter than that in the control group ( P<0.05), and there was no significant difference in hospital stay between the two groups ( P>0.05). There was no intraoperative complication such as acetabular and proximal femoral fractures, neurovascular injuries in both groups, and the incisions healed by first intention. All patients were followed up 2-3 years, with an average of 2.4 years; there was no significant difference in the follow-up time between the two groups ( P>0.05). During the follow-up period, there was no complication such as hip dislocation, wound infection, delayed wound healing, deep venous thrombosis, and hip dislocation in both groups. The hip Harris score and ROM of the two groups gradually increased with time after operation, and the differences were significant when compared with those before operation ( P<0.05); the above two indicators of the study group were significantly better than those of the control group at each time point after operation ( P<0.05). Extensive bone ingrowth on the surface of the components could be observed in the anteroposterior X-ray films of the hip joint of the two groups at 12 months after operation, and the acetabular components was stable without femoral stem subsidence, osteolysis around the components, and heterotopic ossification. At last follow-up, the acetabular component anteversion angle, femoral component anteversion angle, and component combined anteversion angle in the study group were significantly superior to those in the control group ( P<0.05), except that there was no significant difference in the acetabular component abduction angle between the two groups ( P>0.05). Conclusion: For patients with AS affecting the hip joint, the use of the combined anteversion angle technique during THA effectively promotes the recovery of hip joint function and enhances the postoperative quality of life of patients when compared to traditional THA.

Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. METHODS: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation. RESULTS: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. CONCLUSION: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

Successful learning of alpha up-regulation through neurofeedback training modulates sustained attention.

As a fundamental attention function, sustained attention plays a critical role in general cognitive abilities and is closely linked to EEG alpha oscillations. Neurofeedback training (NFT) of alpha activity on different aspects of attention has been studied previously. However, it remains unclear how NFT with up- or down-regulation directions modulates sustained attention. Here we employed a counterbalanced single-blind sham-controlled crossover design, in which healthy young adults underwent one NFT session of alpha up-regulation, one NFT session of alpha down-regulation, and one sham-control NFT session over the posterior area. The session order was counterbalanced with a 7-day interval between each session. After each NFT session, the participants completed a visual continuous temporal expectancy task (vCTET) to assess their sustained attention performance. The results showed that compared to sham-control NFT, successful learning of alpha up-regulation resulted in increased reaction time at the beginning of the attention task but a slower increase over vCTET blocks. On the other hand, successful learning of alpha down-regulation had no impact on attention performance compared to sham-control NFT. These findings suggest that successful learning of alpha up-regulation through NFT could impair initial attention performance but slow down visual attention deterioration over time, i.e., alpha enhancement by NFT stabilizing visual attention.

ADFCNN: Attention-Based Dual-Scale Fusion Convolutional Neural Network for Motor Imagery Brain-Computer Interface.

Convolutional neural networks (CNNs) have been successfully applied to motor imagery (MI)-based brain-computer interface (BCI). Nevertheless, single-scale CNN fail to extract abundant information over a wide spectrum from EEG signals, while typical multi-scale CNNs cannot effectively fuse information from different scales with concatenation-based methods. To overcome these challenges, we propose a new scheme equipped with attention-based dual-scale fusion convolutional neural network (ADFCNN), which jointly extracts and fuses EEG spectral and spatial information at different scales. This scheme also provides novel insight through self-attention for effective information fusion from different scales. Specifically, temporal convolutions with two different kernel sizes identify EEG µ and ß rhythms, while spatial convolutions at two different scales generate global and detailed spatial information, respectively, and the self-attention mechanism performs feature fusion based on the internal similarity of the concatenated features extracted by the dual-scale CNN. The proposed scheme achieves the superior performance compared with state-of-the-art methods in subject-specific motor imagery recognition on BCI Competition IV dataset 2a, 2b and OpenBMI dataset, with the cross-session average classification accuracies of 79.39% and significant improvements of 9.14% on BCI-IV2a, 87.81% and 7.66% on BCI-IV2b, 65.26% and 7.2% on OpenBMI dataset, and the within-session average classification accuracies of 86.87% and significant improvements of 10.89% on BCI-IV2a, 87.26% and 8.07% on BCI-IV2b, 84.29% and 5.17% on OpenBMI dataset, respectively. What is more, ablation experiments are conducted to investigate the mechanism and demonstrate the effectiveness of the dual-scale joint temporal-spatial CNN and self-attention modules. Visualization is also used to reveal the learning process and feature distribution of the model.

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Feedback-related brain activity in individual decision: evidence from a gambling EEG study.

In this study, based on scalp electroencephalogram (EEG), we conducted cortical source localization and functional network analyses to investigate the underlying mechanism explaining the decision processes when individuals anticipate maximizing gambling benefits, particularly in situations where the decision outcomes are inconsistent with the profit goals. The findings shed light on the feedback monitoring process, wherein incongruity between outcomes and gambling goals triggers a more pronounced medial frontal negativity and activates the frontal lobe. Moreover, long-range theta connectivity is implicated in processing surprise and uncertainty caused by inconsistent feedback conditions, while middle-range delta coupling reflects a more intricate evaluation of feedback outcomes, which subsequently modifies individual decision-making for optimizing future rewards. Collectively, these findings deepen our comprehension of decision-making under circumstances where the profit goals are compromised by decision outcomes and provide electrophysiological evidence supporting adaptive adjustments in individual decision strategies to achieve maximum benefit.

A promising electrochemical sensor based on PVP-induced shape control of a hydrothermally synthesized layered structured vanadium disulfide for the sensitive detection of a sulfamethoxazole antibiotic.

The presence of sulfamethoxazole (SMX) in natural waters has become a significant concern recently because of its detrimental effects on human health and the ecological environment. To address this issue, it is of utmost urgency to develop a reliable method that can determine SMX at ultra-low levels. In our research, we utilized PVP-induced shape control of a hydrothermal synthesis method to fabricate layer-like structured VS2, and employed it as an electrode modification material to prepare an electrochemical sensor for the sensitive determination of SMX. Thus, our prepared VS2 electrodes exhibited a linear range of 0.06-10.0 µM and a limit of detection (LOD) as low as 47.0 nM (S/N = 3) towards SMX detection. Additionally, the electrochemical sensor presented good agreement with the HPLC method, and afforded perfect recovery results (97.4-106.8%) in the practical analysis. The results validated the detection accuracy of VS2 electrodes, and demonstrated their successful applicability toward the sensitive determination of SMX in natural waters. In conclusion, this research provides a promising approach for the development of electrochemical sensors based on VS2 composite materials.

Activation network improves spatiotemporal modelling of human brain communication processes.

Dynamic functional networks (DFN) have considerably advanced modelling of the brain communication processes. The prevailing implementation capitalizes on the system and network-level correlations between time series. However, this approach does not account for the continuous impact of non-dynamic dependencies within the statistical correlation, resulting in relatively stable connectivity patterns of DFN over time with limited sensitivity for communication dynamic between brain regions. Here, we propose an activation network framework based on the activity of functional connectivity (AFC) to extract new types of connectivity patterns during brain communication process. The AFC captures potential time-specific fluctuations associated with the brain communication processes by eliminating the non-dynamic dependency of the statistical correlation. In a simulation study, the positive correlation (r=0.966,p<0.001) between the extracted dynamic dependencies and the simulated "ground truth" validates the method's dynamic detection capability. Applying to autism spectrum disorders (ASD) and COVID-19 datasets, the proposed activation network extracts richer topological reorganization information, which is largely invisible to the DFN. Detailed, the activation network exhibits significant inter-regional connections between function-specific subnetworks and reconfigures more efficiently in the temporal dimension. Furthermore, the DFN fails to distinguish between patients and healthy controls. However, the proposed method reveals a significant decrease (p<0.05) in brain information processing abilities in patients. Finally, combining two types of networks successfully classifies ASD (83.636 % ± 11.969 %,mean±std) and COVID-19 (67.333 % ± 5.398 %). These findings suggest the proposed method could be a potential analytic framework for elucidating the neural mechanism of brain dynamics.

Ameliorative effect of anisodamine (654-1/654-2) against myocardial dysfunction induced by septic shock via the NF-κB/NLRP-3 or the PI3K-AKT/NF-κB pathway.

BACKGROUND: Septic shock, an extremely dangerous condition that causes impairment of organ function, always largely contributes to mortality in intensive care units. The impact of septic shock-induced organ damage on morbidity and mortality is substantially influenced by myocardial dysfunction. However, it remains unclear whether and in what manner anisodamine (654-1/654-2) ameliorates myocardial dysfunction caused by septic shock. PURPOSE: This study is the pioneering investigation and validation about the protective efficacy of anisodamine (654-1/654-2) against LPS-induced myocardial dysfunction in septic shock rats. It also aims to explore the differences in the underlying molecular mechanisms of both drugs. METHODS: A septic shock model was established in SD rats by after tail vein administration of LPS. 64 rats were distributed into eight groups, such as LPS group, control group, LPS+654-1 group (1.25, 2.5, and 5 mg/kg), and LPS+654-2 group (1.25, 2.5, and 5 mg/kg). The hemodynamics, echocardiography, immunohistochemical analysis, TEM, TUNEL assay, and H&E staining were utilized to assess the septic shock model and myocardial function. Lactic acid, inflammatory markers (IL-1ß, IL-6, and TNF-α), endothelial injure markers (SDC-1, HS and TM) and myocardial injury markers (CK, c-TNT and NT-pro BNP) were assessed using ELISA or biochemical kits. Additionally, the mechanisms of 654-1/654-2 were analyzed using RNA-seq and bioinformatics, and validated using western blotting and RT-PCR. RESULTS: Administration of 654-1/654-2 significantly restored hemodynamics and improved myocardial and endothelial glycocalyx injury in septic shock rats. Furthermore, 654-1/654-2 dose-dependently reduced plasma levels of lactic acid, inflammatory cytokines, and markers of endothelial and myocardial injury. Analyses using RNA-seq, WB and RT-PCR techniques indicated that 654-1/654-2 could mitigate myocardial and endothelial injury by inhibiting the NF-κB and NLRP-3 pathways, and activating the PI3K-AKT pathway. CONCLUSIONS: These findings demonstrated that 654-1/654-2 could alleviate myocardial damage in septic shock rats. Specifically, 654-1 inhibited the NF-κB/NLRP-3 pathway, whereas 654-2 promoted the PI3K-AKT pathway and inhibited the NF-κB pathway, effectively mitigating the inflammatory response and cell apoptosis.

Steering CO2 Electroreduction Selectivity U-Turn to Ethylene by Cu-Si Bonded Interface.

Copper (Cu), with the advantage of producing a deep reduction product, is a unique catalyst for the electrochemical reduction of CO2 (CO2RR). Designing a Cu-based catalyst to trigger CO2RR to a multicarbon product and understanding the accurate structure-activity relationship for elucidating reaction mechanisms still remain a challenge. Herein, we demonstrate a rational design of a core-shell structured silica-copper catalyst (p-Cu@m-SiO2) through Cu-Si direct bonding for efficient and selective CO2RR. The Cu-Si interface fulfills the inversion in CO2RR product selectivity. The product ratio of C2H4/CH4 changes from 0.6 to 14.4 after silica modification, and the current density reaches a high of up to 450 mA cm-2. The kinetic isotopic effect, in situ attenuated total reflection Fourier-transform infrared spectra, and density functional theory were applied to elucidate the reaction mechanism. The SiO2 shell stabilizes the *H intermediate by forming Si-O-H and inhibits the hydrogen evolution reaction effectively. Moreover, the direct-bonded Cu-Si interface makes bare Cu sites with larger charge density. Such bare Cu sites and Si-O-H sites stabilized the *CHO and activated the *CO, promoting the coupling of *CHO and *CO intermediates to form C2H4. This work provides a promising strategy for designing Cu-based catalysts with high C2H4 catalytic activity.

STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer.

Signal transducer and activator of transcription 4 (STAT4) is a critical transcription factor for T helper cell differentiation and tumor cells. Although its prognostic role and gene function have been reported in several carcinomas, the role of STAT4 in vitro and in vivo in breast cancer remains poorly understood. The effect of STAT4 in immunotherapy is also unclear. Therefore, we integrated bulk transcriptomics, experiments, and single-cell transcriptomics to systematically analyze its function in prognosis and signaling pathway. Several clinical breast cancer cohorts confirmed STAT4 as a T-cell relevant prognostic biomarker. Overexpressed STAT4 increased programmed cell death ligand 1 (PD-L1) and major histocompatibility complex class II levels in breast cancer cells. In molecular mechanism, transcriptional synergy between STAT4 and STAT3 transactivated interleukin (IL)-12R and involved a positive feedback loop: STAT4/IL-12R/JAK2-STAT3-STAT4, which contributed to the upregulation of PD-L1 expression. The above signaling axis was defined as the STAT4-related pathway and its score was used to predict T-cell expansion and anti-PD1 treatment response. These findings highlight a novel molecular mechanism indirectly regulating PD-L1 through the STAT4-related pathway: IL-12R/JAK2-STAT3-STAT4/PD-L1, and it has potential application in predicting anti-PD-1 immunotherapy response, which may pave the way for stratified immunotherapy in breast cancer.

Efficacy and safety of anisodine hydrobromide injection for acute ischemic stroke: a systematic review and meta-analysis.

Background: Acute ischemic stroke (AIS) is a leading cause of death and disability worldwide. This study aimed to evaluate the efficacy and safety of anisodine hydrobromide (Ani) injection in the treatment of AIS. Methods: Randomized controlled trials (RCTs) based on Ani injection for the treatment of AIS were retrieved from both Chinese and English databases. The retrieval period was from the databases' inception to May 2023. The Cochrane Collaboration Risk of Bias Tool was used to assess the methodological quality. The outcome indicators were analyzed using RevMan 5.3 software. Results: We included the findings of 11 RCTs encompassing 1,337 patients with AIS. Our meta-analysis revealed that Ani injection supplementation significantly reduced the National Institutes of Health Stroke Scale [MD = -1.53, 95%CI = (-1.94, -1.12), p < 0.00001], modified Rankin Scale [MD = -0.89, 95%CI = (-0.97, -0.81), p < 0.00001], and the relative time to peak [SMD = -0.81, 95%CI = (-1.08, -0.55), p < 0.00001] significantly. Additionally, Ani injection significantly increased the Barthel Index [MD = 10.65, 95%CI = (4.30, 17.00), p = 0.001], relative cerebral blood volume [SMD = 0.28, 95%CI = (0.02, 0.53), p = 0.03], and clinical efficacy [RR = 1.2, 95%CI = (1.08, 1.34), p = 0.001]. No statistically significant difference in the rate of adverse events was observed between the Ani injection supplemental group and the control group. Conclusion: Based on currently published evidence, Ani injection was found to be effective and safe in improving AIS outcome. Nevertheless, limitations of the included RCTs still exist, and thus, more multi-center, large-sample, high-quality RCTs are required to further verify the efficacy and safety of Ani injection in patients with AIS. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023427591], identifier [PROSPERO 2023 CRD42023427591].