Reference Twice: A Simple and Unified Baseline for Few-Shot Instance Segmentation.

Few-Shot Instance Segmentation (FSIS) requires detecting and segmenting novel classes with limited support examples. Existing methods based on Region Proposal Networks (RPNs) face two issues: 1) Overfitting suppresses novel class objects; 2) Dual-branch models require complex spatial correlation strategies to prevent spatial information loss when generating class prototypes. We introduce a unified framework, Reference Twice (RefT), to exploit the relationship between support and query features for FSIS and related tasks. Our three main contributions are: 1) A novel transformer-based baseline that avoids overfitting, offering a new direction for FSIS; 2) Demonstrating that support object queries encode key factors after base training, allowing query features to be enhanced twice at both feature and query levels using simple cross-attention, thus avoiding complex spatial correlation interaction; 3) Introducing a class-enhanced base knowledge distillation loss to address the issue of DETR-like models struggling with incremental settings due to the input projection layer, enabling easy extension to incremental FSIS. Extensive experimental evaluations on the COCO dataset under three FSIS settings demonstrate that our method performs favorably against existing approaches across different shots, e.g., +8.2/ + 9.4 performance gain over state-of-the-art methods with 10/30-shots. Source code and models will be available at this github site.

Tannic acid as a biphasic modulator of tau protein liquid-liquid phase separation.

Tannic acid (TA) is a natural polyphenol that shows great potential in the field of biomedicine due to its anti-inflammatory, anti-oxidant, anti-bacterial, anti-tumor, anti-virus, and neuroprotective activities. Recent studies have revealed that liquid-liquid phase separation (LLPS) is closely associated with protein aggregation. Therefore, modulating LLPS offers new insights into the treatment of neurodegenerative diseases. In this study, we investigated the influence of TA on the LLPS of the Alzheimer's-related protein tau and the underlying mechanism. Our findings indicate that TA affects the LLPS of tau in a biphasic manner, with initial promotion and subsequent suppression as the TA to tau molar ratio increases. TA modulates tau phase separation through a combination of hydrophobic interactions and hydrogen bonds. The balance between TA-tau and tau-tau interactions is found to be relevant to the material properties of TA-induced tau condensates. We further illustrate that the modulatory activity of TA in phase separation is highly dependent on the target proteins. These findings enhance our understanding of the forces driving tau LLPS under different conditions, and may facilitate the identification and optimization of compounds that can rationally modulate protein phase transition in the future.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

Risk Factors and Prognosis of Perioperative Atrial Fibrillation in Elderly Patients Undergoing VATS Lung Surgery: A Retrospective Cohort Study.

Background: Atrial fibrillation (AF) has become the most common postoperative arrhythmia of thoracic surgery. This study aimed to investigate the risk factors and complications of perioperative atrial fibrillation (PoAF) in elderly patients who underwent video-assisted thoracoscopic surgery (VATS). Methods: Data were collected from patients who underwent VATS between January 2013 and December 2022 at Peking Union Medical College Hospital (PUMCH). Univariable analyses and multivariable logistic regression analyses were used to determine the factors correlated with PoAF. Receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the indicators to predict PoAF. Results: The study enrolled 2920 patients, with a PoAF incidence of 5.2% (95% CI 4.4%-6.0%). In the logistic regression analyses, male sex (OR=1.496, 95% CI 1.056-2.129, P=0.024), left atrial anteroposterior dimension (LAD) ≥40 mm (OR=2.154, 95% CI 1.235-3.578, P=0.004), hypertension (HTN) without regular treatment (OR=2.044, 95% CI 0.961-3.921, P=0.044), a history of hyperthyroidism (OR=4.443, 95% CI 0.947-15.306, P=0.030), surgery of the left upper lobe (compared to other lung lobes) (OR=1.625, 95% CI 1.139-2.297, P=0.007), postoperative high blood glucose (BG) (OR=2.482, 95% CI 0.912-5.688, P=0.048), and the time of chest tube removal (per day postoperatively) (OR=1.116, 95% CI 1.038-1.195, P=0.002) were found to be significantly associated with PoAF. The area under the ROC curve was 0.707 (95% CI 0.519-0.799). 86.9% patients were successfully converted to sinus rhythm. Compared with the non-PoAF group, the PoAF group had significantly greater risks of prolonged air leakage, postoperative acute coronary syndrome, longer ICU stays, and longer hospital stays. Conclusion: Male sex, LAD≥40 mm, HTN without regular treatment, a history of hyperthyroidism, surgery of the left upper lobe, postoperative BG, and the time of chest tube removal were associated with PoAF. These findings may help clinicians identify high-risk patients and take preventive measures to minimize the incidence and adverse prognosis of PoAF.

Incidence of acute Deep Vein Thrombosis in pediatric and adolescent orthopedic trauma hospitalized patients and effect of rivaroxaban treatment.

OBJECTIVE: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT. METHODS: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months. RESULTS: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000). CONCLUSIONS: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT.

Effectiveness and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus: a retrospective comparative study.

Background: This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. Methods: We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. Results: The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. Conclusion: The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

Relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. METHODS: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. RESULTS: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. CONCLUSIONS: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.

Hg2+ removal characteristics of a strain of mercury-tolerant bacteria screened from heavy metal-contaminated soil in a molybdenum-lead mining area.

In this study, the mercury-tolerant strain LTC105 was isolated from a contaminated soil sample collected from a molybdenum-lead mine in Luanchuan County, Henan Province, China. The strain was shown to be highly resistant to mercury, with a minimum inhibitory concentration (MIC) of 32 mg·L-1. After a 24-h incubation in LB medium with 10 mg·L-1 Hg2+, the removal, adsorption, and volatilization rates of Hg2+ were 97.37%, 7.3%, and 90.07%, respectively, indicating that the strain had significant influence on mercury removal. Based on the results of Fourier infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), the investigation revealed that the primary function of LTC105 was to encourage the volatilization of mercury. The LTC105 strain also showed strong tolerance to heavy metals such as Mn2+, Zn2+, and Pb2+. According to the results of the soil incubation test, the total mercury removal rate of the LTC105 inoculation increased by 16.34% when the initial mercury concentration of the soil was 100 mg·L-1 and by 62.28% when the initial mercury concentration of the soil was 50 mg·kg-1. These findings indicate that LTC105 has certain bioremediation ability for Hg-contaminated soil and is a suitable candidate strain for microbial remediation of heavy metal-contaminated soil in mining areas.

Organic Ferroelastic with Dual-Channel Manipulation Obtained by H/F Substitution.

Ferroelastic materials with high phase transition temperature have broad application prospects in information conversion and storage, shape memory, energy conversion, hyperelasticity, etc. However, most of the current reports focus on inorganic ferroelastic materials. Inorganic ferroelastic materials have the disadvantages of high energy consumption and harmful metals, which limit their application in practical work. In contrast, organic ferroelastic materials have the advantages of structural adjustability, environmental protection, easy processing, low cost, mechanical flexibility and so on, which have great development potential in new ferroelastic materials. Here, we have successfully designed and synthesized a pair of homochiral enantiomers [(R/S)-4-fluorobenzoic acid-2-amino-2-phenylethanol](R- and S-F) using the chemical design strategy of H/F substitution. Compared with the non-F substitution[(R/S)-benzoic acid-2-amino-2-phenylethanol] (R- and S-H), they undergo 2F1-type ferroelastic phase transitions at 370 K. Notably, the ferroelastic domains of R/S-F can be controlled through two physical channels that are temperature and stress, showing great potential in dual-channel switches.

Overexpression of REC8 induces aberrant gamete meiotic division and contributes to AML pathogenesis - a multiplexed microarray analysis and mendelian randomization study.

Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia.

Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis.

BACKGROUND: Angiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin-like growth factor (IGF) family is crucial for angiogenesis. Insulin-like growth factor-binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it. METHODS AND RESULTS: IGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R-mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel-Lindau (VHL)-regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post-HLI. CONCLUSION: Our findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis-related conditions.

Detection of the novel HLA-DRB5*01:01:01:07 allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-DRB5*01:01:01:07 differs from HLA-DRB5*01:01:01:01 by two nucleotide changes in intron 1 and intron 2.

Estimation of complete mutual information exploiting nonlinear magnitude-phase dependence: Application to spatial FNC for complex-valued fMRI data.

BACKGROUND: Real-valued mutual information (MI) has been used in spatial functional network connectivity (FNC) to measure high-order and nonlinear dependence between spatial maps extracted from magnitude-only functional magnetic resonance imaging (fMRI). However, real-valued MI cannot fully capture the group differences in spatial FNC from complex-valued fMRI data with magnitude and phase dependence. METHODS: We propose a complete complex-valued MI method according to the chain rule of MI. We fully exploit the dependence among magnitudes and phases of two complex-valued signals using second and fourth-order joint entropies, and propose to use a Gaussian copula transformation with a lower bound property to avoid inaccurate estimation of joint probability density function when computing the joint entropies. RESULTS: The proposed method achieves more accurate MI estimates than the two histogram-based (normal and symbolic approaches) and kernel density estimation methods for simulated signals, and enhances group differences in spatial functional network connectivity for experimental complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with the simplified complex-valued MI and real-valued MI, the proposed method yields higher MI estimation accuracy, leading to 17.4 % and 145.5 % wider MI ranges, and more significant connectivity differences between healthy controls and schizophrenia patients. A unique connection between executive control network (EC) and right frontal parietal areas, and three additional connections mainly related to EC are detected than the simplified complex-valued MI. CONCLUSIONS: With capability in quantifying MI fully and accurately, the proposed complex-valued MI is promising in providing qualified FNC biomarkers for identifying mental disorders such as schizophrenia.

The development of multifunctional materials for water pollution remediation using pollen and sporopollenin.

Pollen is a promising material for water treatment owing to its renewable nature, abundant sources, and vast reserves. The natural polymer sporopollenin, found within pollen exine, possesses a distinctive layered porous structure, mechanical strength, and stable chemical properties, which can be utilized to prepare sporopollenin exine capsules (SECs). Leveraging these attributes, pollen or SECs can be used to develop water pollution remediation materials. In this review, the structure of pollen is first introduced, followed by the categorization of various methods for extracting SECs. Then, the functional expansion of pollen adsorbents, with an emphasis on their recyclability, reusability, and visual sensing capabilities, as opposed to mere functional group modification, is discussed. Furthermore, the progress made in utilizing pollen as a biological template for synthesizing catalysts is summarized. Intriguingly, pollen can also be engineered into self-propelled micromotors, enhancing its potential application in adsorption and catalysis. Finally, the challenges associated with the application of pollen in water pollution treatment are discussed. These challenges include the selection of environmentally friendly, non-toxic reagents in synthesizing pollen water remediation products and the large-scale application after synthesis. Moreover, the multifunctional synthesis and application of different water remediation products are prospected.

Activation of lncRNA DANCR by H3K27 acetylation regulates proliferation of colorectal cancer cells.

The long noncoding DANCR functions as a tumor oncogene in many cancers, including colorectal cancer (CRC). However, the molecular mechanism of DANCR in CRC has not been explored. This study probed the function and potential mechanism by which DANCR contributes to the progression of CRC. The obtained data indicated that DANCR is overexpressed in CRC tissues and cell lines. Knockdown of DANCR hindered CRC cell proliferation, which was mediated by cyclin D1 and CDK4. Bioinformatic analysis, luciferase reporter assays and subcellular fractionation verified that DANCR directly binds to miR-508-5p. Moreover, DANCR acts as a miR-508-5p ceRNA to regulate expression of ATF1. In addition, upregulation of DANCR is attributed to H3K27 acetylation at the promoter region. In conclusion, our study confirmed that activation of lncRNA DANCR by H3K27 acetylation has an oncogenic role in CRC progression and provides a potential therapeutic target for CRC.

Protein disulfide isomerase is essential for spermatogenesis in mice.

Spermatogenesis requires precise posttranslational control in the endoplasmic reticulum (ER), but the mechanism remains largely unknown. The protein disulfide isomerase (PDI) family is a group of thiol oxidoreductases responsible for catalyzing the disulfide bond formation of nascent proteins. In this study, we generated 14 strains of KO mice lacking the PDI family enzymes and found that only PDI deficiency caused spermatogenesis defects. Both inducible whole-body PDI-KO (UBC-Cre/Pdifl/fl) mice and premeiotic PDI-KO (Stra8-Cre/Pdifl/fl) mice experienced a significant decrease in germ cells, testicular atrophy, oligospermia, and complete male infertility. Stra8-Cre/Pdifl/fl spermatocytes had significantly upregulated ER stress-related proteins (GRP78 and XBP1) and apoptosis-related proteins (Cleaved caspase-3 and BAX), together with cell apoptosis. PDI deletion led to delayed DNA double-strand break repair and improper crossover at the pachytene spermatocytes. Quantitative mass spectrometry indicated that PDI deficiency downregulated vital proteins in spermatogenesis such as HSPA4L, SHCBP1L, and DDX4, consistent with the proteins' physical association with PDI in normal testes tissue. Furthermore, PDI served as a thiol oxidase for disulfide bond formation of SHCBP1L. Thus, PDI plays an essential role in protein quality control for spermatogenesis in mice.

Comparative efficacy and safety of JAK/TYK2 inhibitors and other oral drugs for moderate-to-severe plaque psoriasis: A systematic review and network meta-analysis.

Background Janus kinase (JAK)/tyrosine kinase 2 (TYK2) inhibitors are novel treatments for moderate-to-severe plaque psoriasis. Objective To perform a network meta-analysis to compare the efficacy and safety of TYK2 inhibitors with other oral drugs in moderate-to-severe psoriasis. Methods Eligible randomised clinical trials (RCTs) were identified from public databases (published before November 2, 2023). Random-effect frequentist network meta-analysis was performed with ranking based on the surface under the cumulative ranking curve (SUCRA) of Physician's Global Assessment of "clear" or "almost clear" (PGA 0/1), 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75). Results Twenty RCTs containing 7,564 patients with moderate-to-severe psoriasis were included. Deucravacitinib at all dose levels (except for 3 mg every other day) and tofacitinib (10 mg BID) ranked best in achieving PGA 0/1 and PASI-75 at 12- 16 weeks. Tofacitinib (10 mg BID) was considered the most unsafe. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Analysis of Ranking according to efficacy and safety showed deucravacitinib (3 mg QD and 3 mg BID) was the best treatment. Limitations Insufficiency of eligible data and no long-term follow-up data. Conclusion Deucravacitinib showed superior efficacy and safety for treating moderate-to-severe psoriasis over other included drugs.

TGF-ß: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-ß in the microenvironment of multiple myeloma.

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to the TME in the pathogenesis of MM. Many researchers have identified that myeloma cells interact with the components of TME, which is beneficial for their survival, ultimately causing the formation of immunosuppressive and high-metabolism TME. In the process, transforming growth factor-ß (TGF-ß), as a pivotal cytokine in the TME, controls various cells' fates and influences numerous metabolic pathways, including inhibiting immune cells to infiltrate the tumors, suppressing the activation of anti-tumor immune cells, facilitating more immunosuppressive cells, enhancing glucose and glutamine metabolism, dysregulating bone metabolism and so on. Thus, we consider TGF-ß as the tumor promoter. However, in healthy cells and the early stage of tumors, it functions as a tumor suppressor. Due to the effect of context dependence, TGF-ß has dual roles in TME, which attracts us to further explore whether targeting it can overcome obstacles in the treatment of MM by regulating the progression of myeloma, molecular mechanisms of drug resistance, and various signaling pathways in the immune and metabolic microenvironment. In this review, we predominantly discuss that TGF-ß promotes the development of MM by influencing immunity and metabolism.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

ENL reads histone ß-hydroxybutyrylation to modulate gene transcription.

Histone modifications are typically recognized by chromatin-binding protein modules (referred to as 'readers') to mediate fundamental processes such as transcription. Lysine ß-hydroxybutyrylation (Kbhb) is a new type of histone mark that couples metabolism to gene expression. However, the readers that prefer histone Kbhb remain elusive. This knowledge gap should be filled in order to reveal the molecular mechanism of this epigenetic regulation. Herein, we developed a chemical proteomic approach, relying upon multivalent photoaffinity probes to capture binders of the mark, and identified ENL as a novel target of H3K9bhb. Biochemical studies and CUT&Tag analysis further suggested that ENL favorably binds to H3K9bhb, and co-localizes with it on promoter regions to modulate gene expression. Notably, disrupting the interaction between H3K9bhb and ENL via structure-based mutation led to the suppressed expression of genes such MYC that drive cell proliferation. Together, our work offered a chemoproteomics approach and identified ENL as a novel histone ß-hydroxybutyrylation effector that regulates gene transcription, providing new insight into the regulation mechanism and function of histone Kbhb.

Elucidating the binding partners of histone post-translational modifications (hPTMs) is key to understanding epigenetic regulatory pathways. Lysine ß-hydroxybutyrylation (Kbhb) is a novel hPTM that couples metabolism to transcription. However, the effectors reading this mark are poorly understood as the Kbhb-mediated protein­protein interactions are weak and transient. Here, we presented a quantitative chemical proteomics approach using multivalent photoaffinity probes to robustly capture interactors of this mark. Thus, we identified ENL as a novel binder of Kbhb of histone H3 lysine 9 (H3K9bhb). Biochemical studies and CUT&Tag analysis further revealed that ENL recognizes H3K9bhb and co-localizes with it on gene promoters to modulate transcription and tumorigenesis. This study highlights ENL as a histone Kbhb reader for the regulation of transcription.