Label-Free Identification of AML1-ETO Positive Acute Myeloid Leukemia Using Single-Cell Raman Spectroscopy.

Acute myeloid leukemia (AML) is a malignant hematological tumor disease. Chromosomal abnormality is an independent prognostic factor in AML. AML with t(8:21) (q22; q22)/AML1-ETO (AE) is an independent disease group. In this research, a new method based on Raman spectroscopy is reported for label-free single-cell identification and analysis of AE fusion genes in clinical AML patients. Raman spectroscopy reflects the intrinsic vibration information of molecules in a label-free and non-destructive manner, and the fingerprint Raman spectrum of cells characterizes intracellular molecular types and relative concentration information, so as to realize the identification and molecular metabolism analysis of different kinds of cells. We collected the Raman spectra of bone marrow cells from clinically diagnosed AML M2 patients with and without the AE fusion gene. Through comparison of the average spectra and identification analysis based on multivariate statistical methods such as principal component analysis and linear discriminant analysis, the distinction between AE positive and negative sample cells in M2 AML patients was successfully achieved, and the single-cell identification accuracy was more than 90%. At the same time, the Raman spectra of the two types of cells were analyzed by the multivariate curve resolution alternating least squares decomposition method. It was found that the presence of the AE fusion gene may lead to the metabolic changes of lipid and nucleic acid in AML cells, which was consistent with the results of genomic and metabolomic multi-omics studies. The above results indicate that single-cell Raman spectroscopy has the potential for early identification of AE-positive AML.

ARHGAP17 Inhibits Hepatocellular Carcinoma Progression by Inactivation of Wnt/ß-Catenin Signaling Pathway.

As a member of Rho GAPs family, Rho GTPase-Activating Protein 17 (ARHGAP17) regulates cytoskeletal recombination, cell polarity, cell proliferation and cell migration. ARHGAP17 is identified as a tumor suppressor in numerous cancer types. Current study intends to examine ARHGAP17 expression and its possible influence on the progression of hepatocellular carcinoma (HCC). ARHGAP17 expression in HCC cells was verified by RT-PCR and western blot. The proliferation and invasion of HCC cells were evaluated by CCK8 assay and transwell assay, respectively. The mRNA expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, GSK-3ß, Axin1, and APC were detected by RT-PCR. The protein expression of ARHGAP17, PCNA, E-cadherin, N-cadherin, ß-catenin, p-ß-catenin, GSK-3ß, p-GSK-3ß, Axin1, and APC were detected by western blot. ARHGAP17 staining was evaluated by immunohistochemistry and immunofluorescence. ARHGAP17 expression decreased significantly in HCC tumors and HCC cells after EMT. In response to overexpression of ARHGAP17, the capacities of HCC cell proliferation and invasion were reduced significantly, which were also confirmed by tumorigenesis experiments in vivo. With overexpression of ARHGAP17 in HCC cells, the p-GSK3ß/GSK3ß decreased, while the p-ß-catenin/ß-catenin, Axin1 and APC increased. In conclusion, ARHGAP17 inhibits HCC progression by inactivating the Wnt/ß-catenin signaling pathway.

Sandwiched ReS2 nanocables with dual carbon coating for efficient K+/Na+ storage performance.

In this work, the nanocables of few-layered ReS2 nanosheets sandwiched between carbon nanotubes (CNTs) and nitrogen-doped amorphous carbon (NC) coating (i.e., CNT@ReS2@NC) are synthesized as high-performance anodes of both potassium-ion batteries (PIBs) and sodium-ion batteries (SIBs). The CNT@ReS2@NC nanocables with dual carbon modifications have the several advantages for efficient K+/Na+ storage. The few-layered ReS2 nanosheets with a wide interlayer spacing of 0.64 nm contribute to accelerated reaction kinetics for fast K+/Na+ intercalation/extraction. The carbon nanotube skeleton with a hollow interior can effectively relieve the volume change and serve as a robust conductive network to boost structural stability. The NC layer provides rich defects as active sites and suppresses the shuttle effect of polysulfides produced in discharge/charge processes. Consequently, the CNT@ReS2@NC nanocables possess outstanding electrochemical performance in both PIBs and SIBs owing to the synergistic effect from the different components. A long cycling lifespan of 3500 cycles with a maintained discharge capacity of 125 mAh/g is achieved for CNT@ReS2@NC at 1 A/g in PIBs. In SIBs, it can keep a high capacity of 202 mAh/g over 3000 cycles at 5 A/g. Moreover, the CNT@ReS2@NC||Na3V2(PO4)3 full cell can exhibit remarkable cycling performance, yielding a low capacity decay rate of 0.019 % per cycle over 1000 cycles at 2C.

Establishing a protected area network in Xinlong with other effective area-based conservation measures.

Protected areas (PAs) are pivotal to biodiversity conservation, yet their efficacy is compromised by insufficient funding and management. So-called other effective area-based conservation measures (OECMs) present a paradigm shift and address PA limitations. Such measures can expand conservation areas, enhance connectivity, and improve the existing system. To assess the conservation status of biodiversity in Tibetan cultural areas in China, we investigated the spatial distribution of wildlife vulnerable to human disturbance (large- and medium-sized mammals and terrestrial birds) in Xinlong, a traditional Tibetan cultural area. In particular, we compared a PA (Xionglongxi Nature Reserve) and OECMs targeting species conservation. We also investigated the relationship of wildlife with human temporal and spatial activities. The OECMs complemented areas not covered by PA, especially in rich understory biodiversity regions. More species in OECMs tolerated human presence than species in the PA. Existing biodiversity reserves failed to cover areas of high conservation value in Tibet and offered limited protection capacity. Expanding PAs and identifying OECMs improved Xinlong's system by covering most biodiversity hotspots. Building on the tradition of wildlife conservation in Tibet, harnessing OECMs may be an effective means of augmenting biodiversity conservation capacity. We recommend further evaluation of OECMs effectiveness and coverage in Tibetan area as a way to enhance the current PA system.

自然保护地(protected areas, PAs)被认为是生物多样性保护的最重要且最有效的措施之一。然而, 由于资金不足和管理缺失等因素, 自然保护地体系的有效性被大幅度削弱。"其他有效的基于区域的保护措施(other effective area­based conservation measures, OECMs)"引起了基于区域的保护范式转变, 能够有效弥补PAs的不足。OECMs能够有效实现保护面积的扩大, 加强保护地之间的连通性, 完善现有保护地体系。基于此, 为进一步了解中国藏文化地区生物多样性的保护情况, 评估PAs和OECMs在物种保护上的差异。我们以中国新龙县为例, 调查了当地大中型哺乳动物和地栖鸟类这类容易受人为干扰的野生动物的空间分布和与人类互作的时空活动关系。结果表明, 在保护区无法覆盖的区域, OECMs能够提供有效的补充, 如林下区域的生物多样性保护。在OECMs范围内, 更多的物种能够在时空活动上容忍人类的存在, 尤其是猎物物种。在当前生物多样性优先保护区无法涵盖藏区高保护价值区域以及现有保护区保护能力有限的情况下, 藏区野生动物的保护需要采取更多针对性的措施。通过扩大保护区和确定OECMs区域, 能够覆盖新龙绝大部分生物多样性热点地区。鉴于藏区的野生动物保护传统, 借助OECMs的力量是完善和提高藏区生物多样性保护保护能力的有效手段。我们建议未来进一步评估藏区的OECMs的有效性及覆盖情况, 完善自然保护地体系。 基于其他有效的区域保护措施的中国新龙县保护地体系构建.

Stretchable and Breathable Electroluminescent Displays Based on Ultrathin Nanocomposite Designs.

Stretchable electroluminescent devices represent an emerging optoelectronic technology for future wearables. However, their typical construction on sub-millimeter-thick elastomers has limited moisture permeability, leading to discomfort during long-term skin attachment. Although breathable textile displays may partially address this issue, they often have distinct visual appearances with discrete emissions from fibers or fiber junctions. This study introduces a convenient procedure to create stretchable, permeable displays with continuous luminous patterns. The design utilizes ultrathin nanocomposite devices embedded in a porous elastomeric microfoam to achieve high moisture permeability. These displays also exhibit excellent deformability, low-voltage operation, and excellent durability. Additionally, the device is decorated with fluorinated silica nanoparticles to achieve self-cleaning and washable capabilities. The practical implementation of these nanocomposite devices is demonstrated by creating an epidermal counter display that allows intimate integration with the human body. These developments provide an effective design of stretchable and breathable displays for comfortable wearing.

Mental illness and pulmonary tuberculosis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have confirmed that mental illness and pulmonary tuberculosis are closely related and increase each other's incidence; however, whether there is a causal genetic association between the two diseases remains unknown. We attempted to answer this question using bidirectional two-sample Mendelian randomization (MR) in a large cohort study. Method: We performed a bidirectional MR analysis between mental illness (major depressive, anxiety disorder, bipolar disorder, and schizophrenia) and pulmonary tuberculosis using summary statistics from genome-wide association studies in European individuals. The inverse-variance weighted method was used as the primary analytical method to assess causality. In addition, other additional MR methods (weighted median, MR-Egger, and weighted mode) were used to supplement the inverse-variance weighted results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Result: We identified no causal genetic association between mental illness and pulmonary tuberculosis after applying the inverse variance weighted method (major depressive: odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.59-1.71, P = 0.98; anxiety disorder: OR = 1.72, 95% CI = 0.05-67.67, P = 0.76; bipolar disorder OR = 0.89, 95% CI = 0.66-1.22, P = 0.48; and schizophrenia: OR = 1.05, 95% CI = 0.91-1.20, P = 0.51). Similarly, pulmonary tuberculosis was not caustically associated with mental illness (major depressive: OR = 1.01, 95% CI = 1.00-1.02, P = 0.17; anxiety disorder: OR = 1.00, 95% CI = 0.99-1.01, P = 0.06; bipolar disorder: OR = 1.02, 95% CI = 0.98-1.07, P = 0.38; and schizophrenia: OR = 1.01, 95% CI = 0.97-1.05, P = 0.66). Conclusion: Our research does not support a bidirectional causal association between the aforementioned mental illnesses and pulmonary tuberculosis.

Multiple-access ultrastable frequency dissemination based on optical frequency combs via a fiber link.

We demonstrate an optical fiber-based, multiple-access frequency transmission using two optical frequency combs. The experimental results using the Allan deviation analysis show that with the phase compensation technique, the frequency instabilities at the remote site are 8.7 × 10-15/1 s and 1.0 × 10-17/103 s, and at the accessing node along the fiber link, the frequency instabilities are 6.9 × 10-15/1 s and 1.1 × 10-17/103 s. Similarly, the power spectral density of phase noise was analyzed in the frequency domain. These experimental results demonstrate that the compensation scheme improved the performance by two to three orders of magnitude. Thus, the proposed frequency transmission technique has potential application for disseminating ultrastable frequency references in the optical fiber network.

Correlation between serum leptin level and sleep monitoring indexes in patients with obstructive sleep apnea hypopnea syndrome and its predictive value: a cross-sectional analysis.

Objective: To investigate the association between serum leptin (LP) level and polysomnography (PSG) parameters in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A cross-sectional study was conducted. The data of subjects who underwent PSG at hospital between January 2021 and December 2022 were collected retrospectively, 220 participants were included. The subjects were categorized into simple snoring group (n = 45), mild OSAHS group (n = 63), moderate OSAHS group (n = 52), and severe OSAHS group (n = 60). The general characteristics, PSG indices, and serological indices were collected retrospectively. Pearson correlation analysis was used to observe the correlation between serum LP level and PSG parameters. The value of serum LP level in predicting OSAHS was analyzed by receiver operating characteristic curve. Results: The serum LP level was positively correlated with micro-arousal count, micro-arousal index (MAI), high apnea hypopnea index, times of blood oxygen decreased by≥3% and time in saturation lower 90%, and negatively correlated with lowest nocturnal oxygen saturation and mean oxygen saturation (p < 0.05). The area under the curve (AUC) of serum LP level in predicting the occurrence of OSAHS was 0.8276 (95% CI: 0.7713-0.8839), and when the Youden index was 0.587, the sensitivity was 72.00%, and the specificity was 86.67% (p < 0.0001). In the population with high MAI, the AUC of serum LP level in predicting the occurrence of OSAHS was 0.8825 (95% CI: 0.7833-0.9817), and when the Youden index was 0.690, the sensitivity was 79.00% and the specificity was 90.00% (p < 0.0001). Conclusion: Serum LP level is associated with the severity of OSAHS. Serum LP level demonstrates a strong predictive value for the occurrence of OSAHS, particularly in population with high MAI.

Delaying age at first sexual intercourse provides protection against oral cavity cancer: a mendelian randomization study.

Aim: To investigate whether age at first sexual intercourse could lead to any changes in the risk of oral cavity cancer. Methods: A two-sample mendelian randomization was conducted using genetic variants associated with age at first sexual intercourse in UK biobank as instrumental variables. Summary data of Northern American from a previous genome-wide association study aimed at oral cavity cancer was served as outcome. Three analytical methods: inverse variance-weighted, mendelian randomization Egger, and weighted median were used to perform the analysis, among which inverse variance-weighted was set as the primary method. Robustness of the results was assessed through Cochran Q test, mendelian randomization Egger intercept tests, MR PRESSO, leave one out analysis and funnel plot. Results: The primary analysis provided substantial evidence of a positive causal relationship age at first sexual intercourse and the risk of oral cavity cancer (p = 0.0002), while a delayed age at first sexual intercourse would lead to a decreased risk of suffering oral cavity cancer (ß = -1.013). The secondary outcomes confirmed the results (all ß < 0) and all assessments supported the robustness, too (all p > 0.05). Conclusion: The study demonstrates that a delayed sexual debut would provide protection against OCC, thus education on delaying sexual intercourse should be recommended.

Subjective benefits from wearing self-fitting over-the-counter hearing aids in the real world.

Introduction: In 2022, the US Food and Drug Administration enacted final regulations to establish the category of over-the-counter (OTC) hearing aids aimed at reducing barriers to access hearing health care for individuals with self-perceived mild to moderate hearing loss. However, given the infancy of this device category, the effectiveness of OTC hearing aids in real-world environments is not yet well understood. Methods and results: To gain insights into the perceived benefit of self-fitting OTC hearing aids, a two-pronged investigation was conducted. In the primary investigation, 255 active users of a self-fitting OTC hearing aid were surveyed on their perceived benefit using an abridged form of the Satisfaction with Amplification in Daily Living (SADL) scale. The mean global (4.9) and subscale scores (Positive Effect (PE): 4.3; Negative Features (NF): 4.3; Personal Image (PI): 6.1) were within the range of those previously reported for users of prescription hearing aids. In the secondary investigation, 29 individuals with self-reported hearing impairment but no prior experience with the investigational self-fitting OTC hearing aids used the devices and reported their perceived benefit and satisfaction following short-term usage. For this prospective group, the global SADL (5.4) and subscale scores (PE: 4.8; NF: 4.9; PI: 6.5) following a minimum of 10 weeks of real-world use were also within the range of those previously reported for traditional hearing aid users. In addition, this prospective group was also asked quality of life questions which assessed psychological benefits of hearing aid use. Responses to these items suggest hearing aid related improvements in several areas spanning emotional health, relationships at home and at work, social life, participation in group activities, confidence and feelings about one's self, ability to communicate effectively, and romance. Discussion: Converging data from these investigations suggest that self-fitting OTC hearing aids can potentially provide their intended users with a level of subjective benefit comparable to what prescription hearing aid users might experience.

Comparison of electrical microstimulation artifact removal methods for high-channel-count prostheses.

BACKGROUND: Neuroprostheses are used to electrically stimulate the brain, modulate neural activity and restore sensory and motor function following injury or disease, such as blindness, paralysis, and other movement and psychiatric disorders. Recordings are often made simultaneously with stimulation, allowing the monitoring of neural signals and closed-loop control of devices. However, stimulation-evoked artifacts may obscure neural activity, particularly when stimulation and recording sites are nearby. Several methods have been developed to remove stimulation artifacts, but it remains challenging to validate and compare these methods because the 'ground-truth' of the neuronal signals may be contaminated by artifacts. NEW METHOD: Here, we delivered stimulation to the visual cortex via a high-channel-count prosthesis while recording neuronal activity and stimulation artifacts. We quantified the waveforms and temporal properties of stimulation artifacts from the cortical visual prosthesis (CVP) and used them to build a dataset, in which we simulated the neuronal activity and the stimulation artifacts. We illustrate how to use the simulated data to evaluate the performance of six software-based artifact removal methods (Template subtraction, Linear interpolation, Polynomial fitting, Exponential fitting, SALPA and ERAASR) in a CVP application scenario. RESULTS: We here focused on stimulation artifacts caused by electrical stimulation through a high-channel-count cortical prosthesis device. We find that that the Polynomial fitting and Exponential fitting methods outperform the other methods in recovering spikes and multi-unit activity. Linear interpolation and Template subtraction recovered the local-field potentials. CONCLUSION: Polynomial fitting and Exponential fitting provided a good trade-off between the quality of the recovery of spikes and multi-unit activity (MUA) and the computational complexity for a cortical prosthesis.

Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.

Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)3-catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry.

Triglyceride-glucose index and health outcomes: an umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Numerous meta-analyses have explored the association between the triglyceride-glucose (TyG) index and diverse health outcomes, yet the comprehensive assessment of the scope, validity, and quality of this evidence remains incomplete. Our aim was to systematically review and synthesise existing meta-analyses of TyG index and health outcomes and to assess the quality of the evidence. METHODS: A thorough search of PubMed, EMBASE, and Web of Science databases was conducted from their inception through to 8 April 2024. We assessed the quality of reviews using A Measurement Tool to Assess Systematic Reviews (AMSTAR) and the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. This study was registered with PROSPERO (CRD: 42024518587). RESULTS: Overall, a total of 95 associations from 29 meta-analyses were included, investigating associations between TyG index and 30 health outcomes. Of these, 83 (87.4%) associations were statistically significant (P < 0.05) according to the random effects model. Based on the AMSTAR tool, 16 (55.2%) meta-analyses were high quality and none was low quality. The certainty of the evidence, assessed by the GRADE framework, showed that 6 (6.3%) associations were supported by moderate-quality evidence. When compared with the lowest category of the TyG index, the risk of contrast-induced nephropathy (CIN) [relative risk (RR) = 2.25, 95%CI 1.82, 2.77], the risk of stroke in patients with diabetes mellitus (RR = 1.26, 95%CI 1.18, 1.33) or with acute coronary syndrome disease (RR = 1.56, 95%CI 1.06, 2.28), the prognosis of coronary artery disease (CAD)-non-fatal MI (RR = 2.02, 95%CI 1.32, 3.10), and the severity of CAD including coronary artery stenosis (RR = 3.49, 95%CI 1.71, 7.12) and multi-vessel CAD (RR = 2.33, 95%CI 1.59, 3.42) increased with high TyG index. CONCLUSION: We found that the TyG index was positively associated with many diseases including the risk of CIN and stroke, the prognosis of CAD, and the severity of CAD which were supported by moderate-quality evidence. TyG index might be useful to identify people at high-risk for developing these diseases.

The subcommissural organ regulates brain development via secreted peptides.

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. Here, to explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes, Sspo, Car3 and Spdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely, thymosin beta 4, thymosin beta 10 and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.

Pancreatic cancer is a malignancy with high mortality. In addition to the few symptoms until the disease reaches an advanced stage, the high fatality rate is attributed to its rapid development, drug resistance and lack of appropriate treatment. In the selection and research of therapeutic drugs, gemcitabine is the first-line drug for pancreatic cancer. Solving the problem of gemcitabine resistance in pancreatic cancer will contribute to the progress of pancreatic cancer treatment. Long non coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides, play vital roles in cellular physiological metabolic activities. Currently, our group and others have found that some lncRNAs are aberrantly expressed in pancreatic cancer cells, which can regulate the process of cancer through autophagy and Wnt/ß-catenin pathways simultaneously and affect the sensitivity of cancer cells to therapeutic drugs. This review presents an overview of the recent evidence concerning the node of lncRNA for the cross-talk between autophagy and Wnt/ß-catenin signaling in pancreatic cancer, together with the practicability of lncRNAs and the core regulatory factors as targets in therapeutic resistance.

A TH17-intrinsic IL-1ß-STAT5 axis drives steroid resistance in autoimmune neuroinflammation.

Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (TH17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment. Interleukin-1ß (IL-1ß) induced a signal transducer and activator of transcription 5 (STAT5)-mediated steroid-resistant transcriptional program in TH17 cells, which promoted inflammatory cytokine production and suppressed Dex-induced anti-inflammatory genes. TH17-specific deletion of STAT5 ablated the IL-1ß-induced steroid-resistant transcriptional program and rendered EAE mice sensitive to Dex treatment. IL-1ß synergized with Dex to promote the STAT5-dependent expression of CD69 and the development of central nervous system (CNS)-resident CD69+ TH17 cells. Combined IL-1R blockade and Dex treatment ablated CNS-resident TH17 cells, reduced EAE severity, and prevented relapse. CD69+ tissue-resident TH17 cells were also detected in brain lesions of patients with multiple sclerosis. These findings (i) demonstrate that IL-1ß-STAT5 signaling in TH17 cells mediates steroid resistance and (ii) identify a therapeutic strategy for reversing steroid resistance in TH17-mediated CNS autoimmunity.

Impact of nomenclature as metabolic associated steatotic liver disease on steatotic liver disease prevalence and screening: a prospective population survey in Asians.

BACKGROUND AND AIM: The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi-society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. METHOD: We conducted a population-based cross-sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. RESULTS: A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non-MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA-IR (adjusted OR: 1.33, 95% CI: 1.10-2.03) was associated with higher risk of moderate-to-severe steatosis for MASLD non-MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations. CONCLUSION: Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.

Injectable Photothermal PDA/Chitosan/ß-Glycerophosphate Thermosensitive Hydrogels for Antibacterial and Wound Healing Promotion.

Controlling infections while reducing the use of antibiotics is what doctors as well as researchers are looking for. As innovative smart materials, photothermal materials can achieve localized heating under light excitation for broad-spectrum bacterial inhibition. A polydopamine/chitosan/ß-glycerophosphate temperature-sensitive hydrogel with excellent antibacterial ability is synthesized here. Initially, the hydrogel has good biocompatibility. In vitro experiments reveal its noncytotoxic property when cocultured with gingival fibroblasts and nonhemolytic capability. Concurrently, the in vivo biocompatibility is confirmed through liver and kidney blood markers and staining of key organs. Crucially, the hydrogel has excellent photothermal conversion performance, which can realize the photothermal conversion of hydrogel up to 3 mm thickness. When excited by near-infrared light, localized heating is attainable, resulting in clear inhibition impacts on both Staphylococcus aureus and Escherichia coli, with the inhibition rates of 91.22% and 96.69%, respectively. During studies on mice's infected wounds, it is observed that the hydrogel can decrease S. aureus' presence in the affected area when exposed to near-infrared light, and also lessen initial inflammation and apoptosis, hastening tissue healing. These findings provide valuable insights into the design of antibiotic-free novel biomaterials with good potential for clinical applications.