PTBP1-mediated repression of neuron-specific CDC42 splicing constitutes a genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype glioblastoma.

Gene co-expression networks may encode hitherto inadequately recognized vulnerabilities for adult gliomas. By identifying evolutionally conserved gene co-expression modules around EGFR (EM) or PDGFRA (PM), we recently proposed an EM/PM classification scheme, which assigns IDH-wildtype glioblastomas (GBM) into the EM subtype committed in neural stem cell compartment, IDH-mutant astrocytomas and oligodendrogliomas into the PM subtype committed in early oligodendrocyte lineage. Here, we report the identification of EM/PM subtype-specific gene co-expression networks and the characterization of hub gene polypyrimidine tract-binding protein 1 (PTBP1) as a genomic alteration-independent vulnerability in IDH-wildtype GBM. Supervised by the EM/PM classification scheme, we applied weighted gene co-expression network analysis to identify subtype-specific global gene co-expression modules. These gene co-expression modules were characterized for their clinical relevance, cellular origin and conserved expression pattern during brain development. Using lentiviral vector-mediated constitutive or inducible knockdown, we characterized the effects of PTBP1 on the survival of IDH-wildtype GBM cells, which was complemented with the analysis of PTBP1-depedent splicing pattern and overexpression of splicing target neuron-specific CDC42 (CDC42-N) isoform.  Transcriptomes of adult gliomas can be robustly assigned into 4 large gene co-expression modules that are prognostically relevant and are derived from either malignant cells of the EM/PM subtypes or tumor microenvironment. The EM subtype is associated with a malignant cell-intrinsic gene module involved in pre-mRNA splicing, DNA replication and damage response, and chromosome segregation, and a microenvironment-derived gene module predominantly involved in extracellular matrix organization and infiltrating immune cells. The PM subtype is associated with two malignant cell-intrinsic gene modules predominantly involved in transcriptional regulation and mRNA translation, respectively. Expression levels of these gene modules are independent prognostic factors and malignant cell-intrinsic gene modules are conserved during brain development. Focusing on the EM subtype, we identified PTBP1 as the most significant hub for the malignant cell-intrinsic gene module. PTBP1 is not altered in most glioma genomes. PTBP1 represses the conserved splicing of CDC42-N. PTBP1 knockdown or CDC42-N overexpression disrupts actin cytoskeleton dynamics, causing accumulation of reactive oxygen species and cell apoptosis. PTBP1-mediated repression of CDC42-N splicing represents a potential genomic alteration-independent, developmentally conserved vulnerability in IDH-wildtype GBM.

La doped-Fe2(MoO4)3 with the synergistic effect between Fe2+/Fe3+ cycling and oxygen vacancies enhances the electrocatalytic synthesizing NH3.

The electrocatalytic nitrogen reduction reaction (NRR) is a crucial process in addressing energy shortages and environmental concerns by synthesizing the NH3. However, the difficulty of N2 activation and fewer NRR active sites limit the application of NRR. Therefore, the NRR performance can be improved by rapid electron transport paths to participate in multi-electron reactions and N2 activation. Doping with transition metal element is a viable strategy to provide electrons and electronic channels in the NRR. This study focuses on the synthesis of Fe2(MoO4)3 (FeMo) and x%La-doped FeMo (x = 3, 5, 7, and 10) using the hydrothermal method. La-doping creates electron transport channels Fe2+-O2--Fe3+ and oxygen vacancies, achieving an equal molar ratio of Fe2+/Fe3+. This strategy enables the super-exchange in Fe2+-O2--Fe3+, and then enhances electron transport speed for a rapid hydrogenation reaction. Therefore, the synergistic effect of Fe2+/Fe3+ cycling and oxygen vacancies improves the NRR performance. Notably, 5%La-FeMo demonstrates the superior NRR performance (NH3 yield rate: 29.6 µg h-1 mgcat-1, Faradaic efficiency: 5.8%) at -0.8 V (vs. RHE). This work analyzes the influence of the catalyst electronic environment on the NRR performance based on the effect on different valence states of ions on electron transport.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Protocol for preparing mammalian skin samples encompassing hair follicles for spatial transcriptomics.

Spatial transcriptomics enables a single-cell resolution view of gene expression patterns in tissues, providing insight into their biological functions. However, applying this approach to the skin presents inherent challenges. Here, we present a protocol for preparing mammalian skin samples encompassing hair follicles for spatial transcriptomics. We describe steps for sample preparation, embedding, acquisition of frozen slices, RNA quality control, tissue mounting, fixation, staining, and imaging. We then detail procedures for permeabilization, reverse transcription, and cDNA collection. For complete details on the use and execution of this protocol, please refer to Chen et al.1.

Three-Dimensional Covalent Organic Frameworks Based on Linear and Trigonal Linkers for High-Performance H2O2 Photosynthesis.

The design of three-dimensional covalent organic frameworks (3D COFs) using linear and trigonal linkers remains challenging due to the difficulty in achieving a specific non-planar spatial arrangement with low-connectivity building units. Here, we report the novel 3D COFs with linear and trigonal linkers, termed TMB-COFs, exhibiting srs topology. The steric hindrance provides an additional force to alter the torsion angles of peripheral triangular units, guiding the linear unit to connect with the trigonal unit into 3D srs frameworks, rather than the more commonly observed two-dimensional (2D) hcb structures. Furthermore, we comprehensively examined the hydrogen peroxide photocatalytic production capacity of the TMB-COFs in comparison with analogous 2D COFs. The experimental results and DFT calculations demonstrate a significant enhancement in photocatalytic hydrogen peroxide production efficacy through framework regulation. This work emphasizes the steric configuration using low connectivity building units, offering a fresh perspective on the design and application of 3D COFs.

Effects of semaglutide on gut microbiota, cognitive function and inflammation in obese mice.

Objective: This study aims to investigate the effects of semaglutide on gut microbiota, cognitive function, and inflammation in obese mice. Method: Twenty-four C57BL/6J male mice were randomly assigned to three groups: a normal-chow diet group (NCD, n = 8), high-fat diet group (HFD, n = 8), and HFD+semaglutide group (Sema, n = 8). The mice were fed a HFD to establish an animal model of obesity and then administered with semaglutide or saline for 12 weeks. Cognitive function was assessed using the Morris water maze test. Serum pro-inflammatory cytokines were measured. 16S rRNA gene sequencing technology was used to explore gut microbiota characteristics in obese mice. Result: Obese mice showed significant cognitive impairment and inflammation. Semaglutide improved cognitive function and attenuated inflammation induced by a HFD diet. The abundance of gut microbiota was significantly changed in the HFD group, including decreased Akkermansia, Muribaculaceae, Coriobacteriaceae_UCG_002, Clostridia_UCG_014 and increased Romboutsia, Dubosiella, Enterorhabdus. Whereas semaglutide could dramatically reverse the relative abundance of these gut microbiota. Correlation analysis suggested that cognitive function was positively correlated with Muribaculaceae and Clostridia_UCG_014, and negatively associated with Romboutsia and Dubosiella. Romboutsia was positively correlated with TNFα, IL-6 and IL-1ß. While Clostridia_UCG_014 was negatively related to TNFα, IL-6 and IL-1ß. Conclusions: For the first time semaglutide displayed different regulatory effects on HFD-induced gut microbiota dysbiosis. Semaglutide could regulate the structure and composition of gut microbiota associated with cognitive function and inflammation. Thus, affecting gut microbiota might be a potential mechanism of semaglutide in attenuating cognitive function and inflammation.

Neurophysiological effects of cognitive behavioral therapy in social anxiety: An ERP study using a dot-probe task.

BACKGROUND: Social anxious individuals show attention bias towards emotional stimuli, this phenomenon is considered to be an important cause of anxiety generation and maintenance. Cognitive-behavioral therapy (CBT) is a standard psychotherapy for social anxiety disorder. CBT decreases attention biases by correcting the maladaptive beliefs of socially anxious individuals, but it is not clear whether CBT alters neurophysiological features of socially anxious individuals at early automatic and/or late cognitive strategy stage of attentional processing. METHOD: To address this knowledge gap, we collected pre-treatment event-related potential data of 22 socially anxious individuals while they performed a dot-probe task. These participants then received eight weeks of CBT, and post-treatment ERP data were collected after completion of CBT treatment. We also included 29 healthy controls and compared them with individuals with social anxiety to determine the neural mechanisms underlying the effectiveness of CBT. RESULTS: Participants' social anxiety level was significantly alleviated with CBT. ERP results revealed that (1) compared to pre-treatment phase, P1 amplitudes induced by probes significantly decreased at post-treatment phase, whereas P3 amplitudes increased at post-treatment phase; the P1 amplitudes induced by probes following happy-neutral face pairs in socially anxious individuals after treatment was significantly different with that in healthy controls; (2) amplitude of components elicited by face pairs did not change significantly between pre-treatment and post-treatment phases; (3) changes of Liebowitz Social Anxiety Scale were positively correlated with changes of P1 amplitude, and negatively correlated with changes of N1 amplitude. LIMITATIONS: Our sample was university students and lacked randomization, which limits the generalizability of the results. CONCLUSION: The present results demonstrated that CBT may adjust cognitive strategies in the later stage of attentional processing, indicating by changed ERPs appeared in probe-presenting stage for social anxiety.

Cardiac Magnetic Resonance Studies in a Large Animal Model That Simulates the Cardiac Abnormalities of Human Septic Shock.

BACKGROUND: Septic shock is associated with increases in end-diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. METHODS AND RESULTS: Purpose-bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular-arterial coupling, and circumferential strain. Early during sepsis, (0-24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. CONCLUSIONS: The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

Folic acid capping Bi3+-doped Ag quantum dots for enzyme-like dual-mode recognition of toxic S2- and visual sensing of NO2.

BACKGROUND: NO2- and S2- are two kinds of common toxic anions widely distributed in environmental water, soil and food products. Human beings have suffered a lot of diseases from intake of excessive NO2- or S2-, i.e., infantile methemoglobin, cancer and even to death. Although tremendous efforts have been afforded to monitor NO2- and S2-, most were high instrument-depended with complex processing procedures. To keep food safety and to protect human health, it will be a huge challenge to develop a convenient and efficient way to monitor S2- and NO2- in practice. RESULTS: A kind of folic acid capping Bi3+-doped Ag quantum dots (FA@Bi3+-Ag QDs) was developed for the first time by one-pot homogeneous reduced self-assembly. Not only did FA@Bi3+-Ag QDs possess intrinsic fluorescent property, it expressed synergistic peroxidase-like activity to catalyze the redox of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 with Km/vmax of 0.087 mM/6.61 × 10-8 M s-1 and 6.42 mM/6.25 × 10-7 M s-1 respectively. Interestingly, trace S2- could exclusively alter its fluorescent property and peroxidase-like activity, exhibiting significant hypochromic and "turn-on" fluorescent effects. While trace NO2- could make FA@Bi3+-Ag QDs-TMB-H2O2 system hyperchromic. Under the optimized conditions, FA@Bi3+-Ag QDs were applied for dual-mode recognition of S2- and visual sensing of NO2- in real food samples with satisfactory recoveries, i.e., 100.7-107.9 %/95.8-104.7 % and 97.2-104.8 % respectively. The synergistic enzyme-mimic mechanism of FA@Bi3+-Ag QDs and its selective response mechanisms to S2- and NO2- were also proposed. SIGNIFICANCE: This represents the first nanozyme-based FA@Bi3+-Ag QDs system for dual-mode recognition of S2- and visual sensing of NO2-, well meeting the basic requirement in drinking water set by WHO. It will offer a promising way for multi-mode monitoring of different pollution using the same nanozyme-based sensor.

An Integrated Nanoplatform via Dual Channel Excitation for Both Precise Fluorescence Imaging and Photodynamic Therapy of Orthotopic Breast Tumor in NIR-II Region.

Although research on photodynamic therapy (PDT) of malignant tumor has made considerable progress in recent years, it is a remaining challenge to extend PDT to the second near-infrared window (NIR-II) along with real-time and accurate NIR-II fluorescence imaging to determine drug enrichment status and achieve high treatment efficacy. In this work, lanthanide nanoparticles (Ln NPs)-based nanoplatform (LCR) equipped with photosensitizer Chlorin e6 (Ce6) and targeting molecular NH2-PEG1000-cRGDfK are developed, which can achieve NIR-II photodynamic therapy (PDT) and NIR-II fluorescence imaging by dual channel excitation. Under 808 nm excitation, Nd3+ in the outer layer can absorb the energy and transfer inward to emit strong NIR-II emissions (1064 and 1525 nm). Due to the low background noise of NIR-II light and the targeting effect of NH2-PEG1000-cRGDfK, LCR can recognize tiny tumor tissue (≈3 mm) and monitor drug distribution in vivo. Under 1530 nm excitation, internal Er3+ can be self-sensitized, generating intense upconversion emission (662 nm) that can effectively activate Ce6 for in vivo PDT due to the deep tissue penetration of NIR-II light. This study provides a paradigm of theranostic nanoplatform for both real-time fluorescence imaging and PDT of orthotopic breast tumor in NIR-II window.

Novel pleuromutilin derivatives conjugated with phenyl-sulfide and boron-containing moieties as potent antibacterial agents against antibiotic-resistant bacteria.

In response to the escalating threat of microbial resistance, a series of novel pleuromutilin derivatives, conjugated with phenyl-sulfide and boron-containing moieties, were designed and synthesized. Most derivatives, especially 14b and 16b, demonstrated significant efficacy against Gram-positive bacteria, including multidrug-resistant strains, as well as pleuromutilin-resistant strains. Compound 16b showed high stability in the liver microsomes of rats and humans, along with acceptable tolerance in vitro and in vivo. Additionally, compound 16b exhibited promising efficacy in MRSA-infected mouse models. Our data highlight the potential of conjugated pleuromutilin derivatives as valuable agents against drug-resistant bacteria.

Case Report and Literature Review: Orthostatic Hypotension Due to Multiple System Atrophy.

Objective: Multiple system atrophy (MSA) is a rare and fatal adult-onset neurodegenerative disease with multiple clinical and pathological variants. The etiology of MSA remains uncertain. Orthostatic hypotension (OH) is the main characteristic of MSA. An upright position can trigger a syncope attack, making it impossible for the patient to stand and walk briefly. Case Study: We report the case of a 67-year-old man with initial symptoms of recurrent syncope and this patient was hospitalized several times, despite multiple therapeutic interventions, his symptoms persisted. Eventually, this patient died at the age of 68 with a diagnosis of MSA. Conclusion: For those patients with neurogenic OH, an underlying neurodegenerative disease should always be considered. Prompt diagnosis, early aggressive treatment, and prediction of complications may have a huge impact on the prognosis of MSA. This article also reviews relevant reported cases to enrich the experience of treating MSA in the clinic.

Is a Plantarflexed First Ray the Primary Deformity In Children With Cavovarus Feet Secondary to Charcot-Marie-Tooth Disease? A Pedobarographic Analysis.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a common cause of cavovarus foot deformity in children. This deformity is often quoted as being forefoot driven, with a primary deformity of first ray plantarflexion driving the hindfoot into varus by virtue of the tripod effect of the foot, which was hypothesized by Coleman and is commonly assessed clinically using his eponymous block test. The primary goal of this study was to objectively investigate this hypothesis using dynamic pedobarography. METHODS: A review of the gait lab archives at a large tertiary referral center was carried out to identify children with CMT who had foot photos and dynamic pedobarographic data. Two orthopaedic surgeons then determined the weight-bearing hindfoot alignment of these children using clinical photography. The order of contact during gait of the first metatarsal relative to the fifth metatarsal was then obtained from the dynamic pedobarographic data. RESULTS: One hundred eighteen feet from 60 children with CMT met the study inclusion criteria. Sixty-eight varus feet were compared with 50 nonvarus feet. First ray contact occurred before fifth ray contact in only 39.7% of the varus feet compared with 34.0% of the nonvarus feet, which did not meet statistical significance (P=0.526). CONCLUSIONS: In this cohort, dynamic pedobarography did not consistently demonstrate the first metatarsal contact occurring before the fifth metatarsal contact in children with varus feet secondary to CMT. While nearly 40% of the feet did make initial contact on the first ray, 60% of the feet landed in varus before the first ray made contact, leading us to believe that the foot is prepositioned in varus. This may be in part due to the progressive muscle imbalance and secondary deformity that has occurred. Surgical management of these children should take this.

Association between Whole-Grain Intake and Obesity Defined by Different Anthropometric Indicators and Dose-Response Relationship Analysis among U.S. Adults: A Population-Based Study.

Existing research shows an inconsistent correlation between whole-grain intake and obesity risk, with limited study on the dose-response relationship. Here, we aimed to examine this association and dose-response relationship among U.S. adults who participated in a NHANES (2003-2018). The intake of whole grain was collected and calculated from two rounds of 24 h dietary recall. Obesity was categorized based on body mass index (BMI) and waist circumference (WC). Weighted multivariable logistic regression models were used to calculate the odds of obesity according to whole-grain intake, and the dose-response relationship was modeled by restricted cubic spline regression. Among the 27,862 participants, 38.3% had general obesity, while 58.3% had abdominal obesity. After multivariate adjustment of potential confounders, the participants in the highest quintile of whole-grain intake had a lower prevalence of general obesity (OR 0.79; 95% CI 0.72-0.88) and abdominal obesity (OR 0.80; 95% CI 0.73-0.89) compared with those in the lowest category. Spline regression showed an inversely linear dose-response association between whole-grain intake and the prevalence of general obesity and abdominal obesity. In conclusion, a higher whole-grain intake was associated with lower odds of obesity, both general and abdominal. Our findings highlight the importance of increasing the whole-grain intake to prevent and manage obesity.

Berberine as a novel ACSL4 inhibitor to suppress endothelial ferroptosis and atherosclerosis.

The discovery of an inhibitor for acyl-CoA synthetase long-chain family member 4 (ACSL4), a protein involved in the process of cell injury through ferroptosis, has the potential to ameliorate cell damage. In this study, we aimed to investigate the potential of berberine (BBR) as an inhibitor of ACSL4 in order to suppress endothelial ferroptosis and provide protection against atherosclerosis. An atherosclerosis model was created in ApoE-/- mice by feeding a high fat diet for 16 weeks. Additionally, a mouse model with endothelium-specific overexpression of ACSL4 was established. BBR was administered orally to assess its potential therapeutic effects on atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low density lipoprotein (ox-LDL) to simulate atherosclerotic endothelial damage in vitro. The interaction between ACSL4 and BBR has been confirmed, with BBR playing a role in inhibiting erastin-induced ferroptosis by regulating ACSL4. Additionally, BBR has been found to inhibit lipid deposition, plaque formation, and collagen deposition in the aorta, thereby delaying the progression of atherosclerosis. It also restored the abnormal expression of ferroptosis-related proteins in atherosclerotic vascular endothelial cells both in vivo and in vitro. In conclusion, BBR, acting as an ACSL4 inhibitor, can improve atherosclerosis by inhibiting ferroptosis in endothelial cells. This highlights the potential of targeted inhibition of vascular endothelial ACSL4 as a strategy for treating atherosclerosis, with BBR being a candidate for this purpose.

A Tight-Connection g-C3N4/BiOBr (001) S-Scheme Heterojunction Photocatalyst for Boosting Photocatalytic Degradation of Organic Pollutants.

The efficient separation of photogenerated charge carriers and strong oxidizing properties can improve photocatalytic performance. Here, we combine the construction of a tightly connected S-scheme heterojunction with the exposure of an active crystal plane to prepare g-C3N4/BiOBr for the degradation of high-concentration organic pollutants. This strategy effectively improves the separation efficiency of photogenerated carriers and the number of active sites. Notably, the synthesized g-C3N4/BiOBr displays excellent photocatalytic degradation activity towards various organic pollutants, including methylene blue (MB, 90.8%), congo red (CR, 99.2%), and tetracycline (TC, 89%). Furthermore, the photocatalytic degradation performance of g-C3N4/BiOBr for MB maintains 80% efficiency under natural water quality (tap water, lake water, river water), and a wide pH range (pH = 4-10). Its excellent photocatalytic activity is attributed to the tight connection between g-C3N4 and BiOBr in the S-scheme heterojunction interface, as well as the exposure of highly active (001) crystal planes. These improve the efficiency of the separation of photogenerated carriers, and maintain their strong oxidation capability. This work presents a simple approach to improving the separation of electrons and holes by tightly combining two components within a heterojunction.

Covalent Organic Frameworks for Electrocatalysis：Design, Applications, and Perspectives.

Covalent organic frameworks (COFs) are an innovative class of crystalline porous polymers composed of light elements such as C, N, O, etc., linked by covalent bonds. The distinctive properties of COFs, including designable building blocks, large specific surface area, tunable pore size, abundant active sites, and remarkable stability, have led their widespread applications in electrocatalysis. In recent years, COF-based electrocatalysts have made remarkable progress in various electrocatalytic fields, including the hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, nitrogen reduction reaction, nitrate reduction reaction, and carbon dioxide reduction reaction. This review begins with an introduction to the design and synthesis strategies employed for COF-based electrocatalysts. These strategies include heteroatom doping, metalation of COF and building monomers, encapsulation of active sites within COF pores, and the development of COF-based derived materials. Subsequently, a systematic overview of the recent advancements in the application of COF-based catalysts in electrocatalysis is presented. Finally, the review discusses the main challenges and outlines possible avenues for the future development of COF-based electrocatalysts.

Effects of exoskeleton-assisted walking on bowel function in motor-complete spinal cord injury patients: involvement of the brain-gut axis, a pilot study.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p <0.05). The EAW group showed an increasing trend in the neurogenic bowel dysfunction (NBD) score after 8 weeks of training, while the conventional group showed a worsening trend. Patients who received the EAW intervention exhibited a decreased abundance of Bacteroidetes and Verrucomicrobia, while Firmicutes, Proteobacteria, and Actinobacteria were upregulated. In addition, there were decreases in the abundances of Bacteroides, Prevotella, Parabacteroides, Akkermansia, Blautia, Ruminococcus 2, and Megamonas. In contrast, Ruminococcus 1, Ruminococcaceae UCG002, Faecalibacterium, Dialister, Ralstonia, Escherichia-Shigella, and Bifidobacterium showed upregulation among the top 15 genera. The abundance of Ralstonia was significantly higher in the EAW group than in the conventional group, and Dialister increased significantly in EAW individuals at 8 weeks. This study suggests that EAW can improve intestinal function of SCI patients in a limited way, and may be associated with changes in the abundance of intestinal flora, especially an increase in beneficial bacteria. In the future, we need to further understand the changes in microbial groups caused by EAW training and all related impact mechanisms, especially intestinal flora metabolites. Clinical trial registration: https://www.chictr.org.cn/.

Sleep traits and breast cancer risk: a two-sample Mendelian randomization study.

Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Exploring optimal incubation conditions and characteristics of methane oxidizing organisms in deep-sea environments.

Anaerobic methanotrophic archaea (ANME) play key roles in buffering the methane budget in the deep-sea environment. This study aimed to explore the optimal environmental conditions for ANME enrichment. The result showed that the sample at 10.5 MPa contained the largest copy numbers of methyl-coenzyme M reductase alpha subunit (mcrA) gene (1.1 × 106 copies/g) compared to any other pressures and the sample at 4 °C contained higher mcrA gene (1.6 × 106 copies/g) than other temperatures. The optimal enrichment pressure for ANME-2c is 10.5 MPa at 4 °C, with an optimal subsequent incubation for ANME-2c less than 211days. Moreover, the beta nearest taxon index was significantly correlated with the incubation time (P<0.05). Total inorganic carbon and sulfate ion were key environmental factors driving community construction. This study offers insights into how ANME-2c was enriched and how species coexist in shared habitats during enrichment.