Methyltransferase Setd2 prevents T cell-mediated autoimmune diseases via phospholipid remodeling.

Coordinated metabolic reprogramming and epigenetic remodeling are critical for modulating T cell function and differentiation. However, how the epigenetic modification controls Th17/Treg cell balance via metabolic reprogramming remains obscure. Here, we find that Setd2, a histone H3K36 trimethyltransferase, suppresses Th17 development but promotes iTreg cell polarization via phospholipid remodeling. Mechanistically, Setd2 up-regulates transcriptional expression of lysophosphatidylcholine acyltransferase 4 (Lpcat4) via directly catalyzing H3K36me3 of Lpcat4 gene promoter in T cells. Lpcat4-mediated phosphatidylcholine PC(16:0,18:2) generation in turn limits endoplasmic reticulum stress and oxidative stress. These changes decrease HIF-1α transcriptional activity and thus suppress Th17 but enhance Treg development. Consistent with this regulatory paradigm, T cell deficiency of Setd2 aggravates neuroinflammation and demyelination in experimental autoimmune encephalomyelitis due to imbalanced Th17/Treg cell differentiation. Overall, our data reveal that Setd2 acts as an epigenetic brake for T cell-mediated autoimmunity through phospholipid remodeling, suggesting potential targets for treating neuroinflammatory diseases.

Astrocytes Modulate a Specific Paraventricular Thalamus→Prefrontal Cortex Projection to Enhance Consciousness Recovery from Anesthesia.

Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of the paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of the PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on the PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVT→prefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which is mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.

Modulating Nucleation and Crystal Growth of Tin Perovskite Films for Efficient Solar Cells.

The performance of tin halide perovskite solar cells (PSCs) has been severely limited by the rapid crystallization of tin perovskites, which usually leads to an undesirable film quality. In this work, we tackle this issue by regulating the nucleation and crystal growth of tin perovskite films using a small Lewis base additive, urea. The urea-SnI2 interaction facilitates the formation of larger and more uniform clusters, thus accelerating the nucleation process. Additionally, the crystal growth process is extended, resulting in a high-quality tin perovskite film with compact morphology, increased crystallinity, and reduced defects. Consequently, the efficiency of tin PSCs is significantly increased from 10.42% to 14.22%. This work highlights the importance of manipulating the nucleation and crystal growth of tin perovskites to realize efficient tin PSCs.

Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Fatty liver disease protective MTARC1 p.A165T variant reduces the protein stability of MTARC1.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of liver disease worldwide. MTARC1, encoded by the MTARC1 gene, is a mitochondrial outer membrane-anchored enzyme. Interestingly, the MTARC1 p.A165T (rs2642438) variant is associated with a decreased risk of NAFLD, indicating that MTARC1 might be an effective target. It has been reported that the rs2642438 variant does not have altered enzymatic activity so we reasoned that this variation may affect MTARC1 stability. In this study, MTARC1 mutants were generated and stability was assessed using a protein stability reporter system both in vitro and in vivo. We found that the MTARC1 p.A165T variant has dramatically reduced the stability of MTARC1, as assessed in several cell lines. In mice, the MTARC1 A168T mutant, the equivalent of human MTARC1 A165T, had diminished stability in mouse liver. Additionally, several MTARC1 A165 mutants, including A165S, A165 N, A165V, A165G, and A165D, had dramatically decreased stability as well, suggesting that the alanine residue of MTARC1 165 site is essential for MTARC1 protein stability. Collectively, our data indicates that the MTARC1 p.A165T variant (rs2642438) leads to reduced stability of MTARC1. Given that carriers of rs2642438 show a decreased risk of NAFLD, the findings herein support the notion that MTARC1 inhibition may be a therapeutic target to combat NAFLD.

Homogenizing The Low-Dimensional Phases for Stable 2D-3D Tin Perovskite Solar Cells.

2D-3D tin-based perovskites are considered as promising candidates for achieving efficient lead-free perovskite solar cells (PSCs). However, the existence of multiple low-dimensional phases formed during the film preparation hinders the efficient transport of charge carriers. In addition, the non-homogeneous distribution of low-dimensional phases leads to lattice distortion and increases the defect density, which are undesirable for the stability of tin-based PSCs. Here, mixed spacer cations [diethylamine (DEA+) and phenethylamine (PEA+)] are introduced into tin perovskite films to modulate the distribution of the 2D phases. It is found that compared to the film with only PEA+, the combination of DEA+ and PEA+ favors the formation of homogeneous low-dimensional perovskite phases with three octahedral monolayers (n = 3), especially near the bottom interface between perovskite and hole transport layer. The homogenization of 2D phases help improve the film quality with reduced lattice distortion and released strain. With these merits, the tin PSC shows significantly improved stability with 94% of its initial efficiency retained after storing in a nitrogen atmosphere for over 4600 h, and over 80% efficiency maintained after continuous illumination for 400 h.

Is pharmacologic venous Thromboprophylaxis necessary for patients undergoing minimally invasive surgery for endometrial Cancer? A systematic review and Meta-analysis.

OBJECTIVE: Given the low incidence of venous thromboembolism (VTE) in endometrial cancer patients undergoing minimally invasive surgery, coupled with the existing uncertainties within guidelines regarding pharmacologic thromboprophylaxis in this area, there is an urgent need for a comprehensive literature review. This review aims to evaluate the necessity of pharmacologic VTE prophylaxis in these patients. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov were systematically searched from inception to March 10, 2024. The analysis was performed using R version 4.2.3. RESULTS: Seven studies involving 3931 endometrial cancer patients were included in the analysis. Meta-analysis results revealed that within 30 days postoperatively, the incidence of VTE was 0.51% (5 out of 990) in the pharmacologic prophylaxis group and 0.70% (7 out of 995) in the mechanical prophylaxis group, with a relative risk (RR) of 1.14 (95% CI 0.19-6.95), indicating no significant difference between the groups. Additionally, within the same timeframe, the incidence of VTE was 0.37% (4 out of 1083) in the extended pharmacologic prophylaxis group and 1.14% (4 out of 352) in the non-extended pharmacologic prophylaxis group, yielding an RR of 0.41 (95% CI 0.11-1.54), again showing no significant difference between the groups. CONCLUSIONS: Our study indicates that routine pharmacological VTE prophylaxis may not be imperative for endometrial cancer patients undergoing minimally invasive surgery, as mechanical prophylaxis alone seems to be efficacious. However, it is crucial to acknowledge that a subset of high-risk patients may derive benefit from pharmacological prophylaxis or even extended regimens. Nonetheless, the absence of a validated risk prediction model for identifying such patients underscores the need for further research in this area. PROTOCOL REGISTRATION: CRD 42024516595.

Prognostic value of three-tiered scoring system for lymph-vascular space invasion in endometrial cancer: A systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of lymph-vascular space invasion (LVSI) status on the prognosis of endometrial cancer (EC) according to a three-tiered scoring system for LVSI. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to September 1st, 2023. The analysis was conducted using STATA 16.0. RESULTS: A total of 9 studies with 4456 EC patients were included in the analysis. No LVSI was found in 72% of EC patients (95% CI 0.65-0.79), while focal and substantial LVSI were present in 16% (95% CI 0.11-0.21) and 13% (95% CI 0.08-018) of patients, respectively. Compared to the no LVSI group, the focal and substantial LVSI groups had poorer overall survival (for focal LVSI: HR 1.33, 95% CI 1.02-1.74; for substantial LVSI: HR 2.51, 95% CI 1.61-3.90), poorer disease-free survival (for substantial LVSI: HR 2.86, 95% CI 1.21-6.77), and an increased risk of recurrence, including pelvic recurrence (for focal LVSI: HR 2.05, 95% CI 1.03-4.07; for substantial LVSI: HR 6.06, 95% CI 3.31-11.08), distant recurrence (for focal LVSI: HR 2.04, 95% CI 1.42-2.92; for substantial LVSI: HR 3.36, 95% CI 2.35-4.793), and lymph node involvement (for focal LVSI: OR 3.52, 95% CI 1.339.34; for substantial LVSI: OR 5.42, 95% CI 2.78-10.58). Substantial LVSI was more prone to pelvic recurrence (HR 1.82, 95% CI 1.05-3.15) and distant recurrence (HR 2.21, 95% CI 1.48-3.28) than focal LVSI. CONCLUSIONS: EC patients with focal and substantial LVSI had poorer survival, recurrence, and a higher incidence of lymph node metastasis than patients without LVSI. The substantial LVSI group was associated with even worse prognosis than the focal LVSI group. The three-tiered LVSI scoring system might effectively predict the prognosis of EC and guide clinical decision-making. PROTOCOL REGISTRATION: CRD 42023451793.

Changes in information integration and brain networks during propofol-, dexmedetomidine-, and ketamine-induced unresponsiveness.

BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.

Splenectomy as a part of cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

OBJECTIVE: The role of splenectomy on cytoreductive surgery in patients with ovarian cancer remains controversial. We conducted this meta-analysis to evaluate the safety and impact of survival outcome of splenectomy in patients with ovarian cancer. METHODS: In this meta-analysis we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to November 10, 2023. RESULT: This meta-analysis included 10 studies, totaling 6297 patients, comprising one prospective and nine retrospective analyses. The results indicated no significant disparity in overall survival and mortality (OR 1.14, 95% CI 0.69 to 1.87, p=0.62) between the splenectomy cohort and the no splenectomy (required) cohort. Furthermore, relative to the no splenectomy (required) cohort, the splenectomy group showed a heightened incidence of overall post-operative complications (odds ratio (OR) 1.66, 95% CI 1.65 to 2.61, p=0.03), an extended duration of hospitalization (mean difference (MD) 2.88 days, 95% CI 2.09 to 3.67), an increased interval from surgery to the initiation of adjuvant chemotherapy (MD 4.44 days, 95% CI 2.41 to 6.07, p<0.0001), and a greater probability of undergoing reoperation (OR 4.7, 95% CI 1.91 to 11.55, p=0.0007). However, concerning the occurrence of specific post-operative complications such as anastomotic leakage (OR 0.97, 95% CI 0.33 to 2.84, p=0.95), pancreatic fistula (OR 3.25, 95% CI 0.63 to 16.7, p=0.16), abdominal abscess (OR 1.75, 95% CI 0.25 to 12.33, p=0.57), sepsis (OR 1.46, 95% CI 0.77 to 2.77, p=0.25), and thrombotic events (OR 1.82, 95% CI 0.93 to 3.57, p=0.08), no significant differences were observed between the two cohorts. CONCLUSION: Splenectomy does not impact the overall survival and mortality of patients with ovarian cancer. Thus, it can be considered an acceptably safe procedure to obtain optimal cytoreduction. However, caution should be taken when selecting patients for splenectomy because it is associated with an increased incidence of overall post-operative complications, prolonged hospital stays, delayed initiation of adjuvant chemotherapy, and an increased probability of requiring subsequent surgical interventions.

Risk factors for postoperative urinary retention in patients underwent surgery for benign anorectal diseases: a nested case-control study.

BACKGROUND: Postoperative urinary retention (POUR) is a common complication of anorectal surgery. This study was to determine the incidence of POUR in anorectal surgery for benign anorectal diseases, identify its risk factors, and establish a nomogram for prediction of POUR. METHODS: A nested case-control study was conducted. The clinical data of patients were collected, and the incidence of POUR was analyzed. Univariate analysis was used to identify the risk factors associated with POUR, and multivariate logistic regression analysis was used to determine independent risk factors for POUR. A nomogram for the preoperative prediction of POUR using a logistic regression model was developed (n = 609). RESULTS: The incidence of POUR after anorectal surgery for benign anorectal diseases was 19.05%. The independent risk factors for POUR were: female (P = 0.007); male with benign prostatic hyperplasia (BPH) (P = 0.001); postoperative visual analogue scale (VAS) score > 6 (P = 0.002); patient-controlled epidural analgesia (PCEA) (P = 0.016); and a surgery time > 30 min (P = 0.039). In the nomogram, BPH is the most important factor affecting the occurrence of POUR, followed by a postoperative VAS score > 6, PCEA, surgery time > 30 min, and sex has the least influence. CONCLUSION: For patients undergoing anorectal surgery for benign anorectal diseases, preventive measures can be taken to reduce the risk of POUR, taking into account the following risk factors: female or male with BPH, severe postoperative pain, PCEA, and surgery time > 30 min. Furthermore, we developed and validated an easy-to-use nomogram for preoperative prediction of POUR in anorectal surgery for benign anorectal diseases. TRIAL REGISTRATION: China Clinical Trial Registry: ChiCTR2000039684, 05/11/2020.

Application of machine learning approaches to predict ammonium nitrogen transport in different soil types and evaluate the contribution of control factors.

The loss of nitrogen in soil damages the environment. Clarifying the mechanism of ammonium nitrogen (NH4+-N) transport in soil and increasing the fixation of NH4+-N after N application are effective methods for improving N use efficiency. However, the main factors are not easily identified because of the complicated transport and retardation factors in different soils. This study employed machine learning (ML) to identify the main influencing factors that contribute to the retardation factor (Rf) of NH4+-N in soil. First, NH4+-N transport in the soil was investigated using column experiments and a transport model. The Rf (1.29 - 17.42) was calculated and used as a proxy for the efficacy of NH4+-N transport. Second, the physicochemical parameters of the soil were determined and screened using lasso and ridge regressions as inputs for the ML model. Third, six machine learning models were evaluated: Adaptive Boosting, Extreme Gradient Boosting (XGB), Random Forest, Gradient Boosting Regression, Multilayer Perceptron, and Support Vector Regression. The optimal ML model of the XGB model with a low mean absolute error (0.81), mean squared error (0.50), and high test r2 (0.97) was obtained by random sampling and five-fold cross-validation. Finally, SHapely Additive exPlanations, entropy-based feature importance, and permutation characteristic importance were used for global interpretation. The cation exchange capacity (CEC), total organic carbon (TOC), and Kaolin had the greatest effects on NH4+-N transport in the soil. The accumulated local effect offered a fundamental insight: When CEC > 6 cmol+ kg-1, and TOC > 40 g kg-1, the maximum resistance to NH4+-N transport within the soil was observed. This study provides a novel approach for predicting the impact of the soil environment on NH4+-N transport and guiding the establishment of an early-warning system of nutrient loss.

The Study of Remazolam Combined With Propofol on Painless Gastroscopy: A Randomized Controlled Trial.

PURPOSE: Gastroscopy is one of the most commonly used diagnostic modalities for upper gastrointestinal disorders. Remazolam besylate, a new type of ultrashort-acting benzodiazepine drug, has been less studied in gastroscopy. In this study, we studied the efficacy and safety of remazolam combined with propofol for painless gastroscopy. DESIGN: This was a single-center, placebo-controlled randomized trial. METHODS: One hundred patients undergoing painless gastroscopy were included in this study and randomly divided into 2 groups (n = 50 per group): the control group (Con group) and the remazolam group (Rem group). Sufentanil, remazolam, and propofol were used to anesthetize the patients, and then, the effects of different solutions on these patients were compared and analyzed. The patient's general condition, vital signs at different times, the dosage of propofol (mg) and additional times, complications, duration of gastroscopy (minutes), recovery time (minutes), length of stay in the recovery room (minutes), and adverse reactions were recorded. FINDINGS: Rem group systolic blood pressure was more stable (P < .05). The amount of additional propofol in Rem group was less (P < .05). The incidence of hypotension, bradycardia, and dizziness was lower in Rem group, as well as the time of awakening and stay in the recovery room were shorter (P < .05). CONCLUSIONS: Remazolam combined with sufentanil and propofol has less effect on hemodynamics in painless gastroscopy, and the patients have shorter awakening times.

[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Ambient Air Processed Inverted Inorganic Perovskite Solar Cells with over 21 % Efficiency Enabled by Multifunctional Ethacridine Lactate.

All-inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2-filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture-induced black-to-yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p-i-n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I- and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08 %. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all-inorganic PSCs.

Emerging mechanisms of ferroptosis and its implications in lung cancer.

ABSTRACT: Lung cancer is one of the most common malignancies and has the highest number of deaths among all cancers. Despite continuous advances in medical strategies, the overall survival of lung cancer patients is still low, probably due to disease progression or drug resistance. Ferroptosis is an iron-dependent form of regulated cell death triggered by the lethal accumulation of lipid peroxides, and its dysregulation is implicated in cancer development. Preclinical evidence has shown that targeting the ferroptosis pathway could be a potential strategy for improving lung cancer treatment outcomes. In this review, we summarize the underlying mechanisms and regulatory networks of ferroptosis in lung cancer and highlight ferroptosis-targeting preclinical attempts to provide new insights for lung cancer treatment.

Clinical application of tranexamic acid in arthroscopic rotator cuff repair surgery: A randomized controlled trial.

BACKGROUND: To investigate whether intravenous administration of tranexamic acid (TXA) prior to arthroscopic rotator cuff repair improves operative blood loss, postoperative fibrinolytic index, inflammatory response, and postoperative pain. METHODS: This was a prospective, double-blind, randomized controlled study. From January 2023 to February 2024, 64 patients who required arthroscopic rotator cuff repair were included and divided into tranexamic acid group (T group) group and control group (C group) according to the random number table method. In T group, 1000 mg TXA was administered intravenously 10 minutes before surgery, and an equivalent dose of normal saline was administered intravenously 10 minutes before surgery in C group. Intraoperative bleeding, postoperative fibrinolytic indexes, inflammatory indexes, pain scores, and occurrence of adverse effects were compared between the 2 groups. RESULTS: Intraoperative bleeding in T group was lower than that in C group (P < .05); D-D and FDP in T group were significantly lower than those in C group (P < .05); postoperative TNF-α and IL-6 in 2 groups was higher than that before operation and T group was lower than C group (P < .05); The pain scores of the 2 groups after operation were lower than those before operation (P < .05), and there was no difference between the 2 groups (P > .05). CONCLUSION SUBSECTIONS: TXA is able to reduce blood loss and inflammatory reactions, modulate fibrinolytic function, and promote postoperative recovery in patients undergoing arthroscopic rotator cuff repair, with no elevated risk of complications.

Targeting bromodomian-containing protein 8 (BRD8): An advanced tool to interrogate BRD8.

Epigenetic modifications play crucial roles in physiological processes, including cell differentiation, proliferation, and death. Bromodomain/Brd-containing proteins (BCPs) regulate abnormal gene expression in various diseases by recognizing the lysine-ε-N-acetylated residues (KAc) or by acting as transcriptional co-activators. Small molecule inhibitors targeting BCPs offer an attractive strategy for modulating aberrant gene expression. Besides the extensive research on the bromodomain and extra-terminal (BET) domain family proteins, the non-BET proteins have gained increasing attention. Bromodomain containing protein 8 (BRD8), a reader of KAc and co-activator of nuclear receptors (NRs), plays a key role in various cancers. This review provides a comprehensive analysis of the structure, disease-related functions, and inhibitor development of BRD8. Opportunities and challenges for future studies targeting BRD8 in disease treatment are discussed.

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.

ABSTRACT: Glial cells play crucial roles in regulating physiological and pathological functions, including sensation, the response to infection and acute injury, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system, and satellite glial cells and Schwann cells in the peripheral nervous system. Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models, few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord. Here, we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these findings with those from mice. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were each divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into five, four, and five distinct transcriptomic subclusters, respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice. Additionally, we detected sex differences in gene expression in human spinal cord glial cells. Specifically, in all astrocyte subtypes, the levels of NEAT1 and CHI3L1 were higher in males than in females, whereas the levels of CST3 were lower in males than in females. In all microglial subtypes, all differentially expressed genes were located on the sex chromosomes. In addition to sex-specific gene differences, the levels of MT-ND4, MT2A, MT-ATP6, MT-CO3, MT-ND2, MT-ND3, and MT-CO2 in all spinal cord oligodendrocyte subtypes were higher in females than in males. Collectively, the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cord-related illnesses, including chronic pain, amyotrophic lateral sclerosis, and multiple sclerosis.