Research Note: Pharmacokinetics of bromhexine hydrochloride in broilers after single oral and intravenous administration.

The current study aimed to investigate the pharmacokinetics of bromhexine hydrochloride in broilers after single intravenous (IV) and oral (PO) administration at 2.5 mg/kg body weight (BW). The trial adopted a randomized, parallel-controlled design, where 20 twelve-wk-old broilers were randomly assigned to either the PO or IV group. Blood samples were collected at predetermined time points, and plasma was further separated for analysis. The bromhexine hydrochloride concentrations in plasma samples were determined using an ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method. Noncompartmental analysis (NCA) using Phoenix software was conducted to analyze the concentration versus time data of bromhexine hydrochloride in every chicken. Subsequently, the main pharmacokinetic parameters between the 2 groups were statistically analyzed using SPSS software. Results from NCA revealed that after oral administration at 2.5 mg/kg BW, bromhexine hydrochloride exhibited slow absorption, reaching an average peak concentration of 32.72 ng/mL at 1.78 h. However, incomplete absorption was observed, with an absolute bioavailability of only 20.06% ± 10.84%. Additionally, bromhexine hydrochloride displayed wide distribution, with a steady-state distribution volume (VSS) of 22.55 ± 13.45 L/kg, and slow elimination, with a clearance (Cl) of 1.52 ± 0.38 L/h/kg. Furthermore, gender effects were assessed on the pharmacokinetics of bromhexine hydrochloride in broilers, revealing better absorption in male broilers compared to females. This disparity may be attributed to the faster blood flow and richer blood volume typically found in male broilers.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

BACKGROUND: Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. OBJECTIVES: This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. METHODS: We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER, ≥5% absolute LVEF increase) were assessed at 6 months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. RESULTS: There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0 to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P = 0.037), with more than 3-fold increased odds of ER (odds ratio: 4.35; P = 0.033). In high sepal scar subgroups (≥5.7%, range: 5.7% to 65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P = 0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P = 0.002) and LVEF improvement (P = 0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8 to 42.1) months, the composite clinical outcome occurred in 34.7% (n = 51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. CONCLUSIONS: Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Improving the estimation of rice above-ground biomass based on spatio-temporal UAV imagery and phenological stages.

Introduction: Unmanned aerial vehicles (UAVs) equipped with visible and multispectral cameras provide reliable and efficient methods for remote crop monitoring and above-ground biomass (AGB) estimation in rice fields. However, existing research predominantly focuses on AGB estimation based on canopy spectral features or by incorporating plant height (PH) as a parameter. Insufficient consideration has been given to the spatial structure and the phenological stages of rice in these studies. In this study, a novel method was introduced by fully considering the three-dimensional growth dynamics of rice, integrating both horizontal (canopy cover, CC) and vertical (PH) aspects of canopy development, and accounting for the growing days of rice. Methods: To investigate the synergistic effects of combining spectral, spatial and temporal parameters, both small-scale plot experiments and large-scale field testing were conducted in Jiangsu Province, China from 2021 to 2022. Twenty vegetation indices (VIs) were used as spectral features, PH and CC as spatial parameters, and days after transplanting (DAT) as a temporal parameter. AGB estimation models were built with five regression methods (MSR, ENet, PLSR, RF and SVR), using the derived data from six feature combinations (VIs, PH+CC, PH+CC+DAT, VIs+PH +CC, VIs+DAT, VIs+PH+CC+DAT). Results: The results showed a strong correlation between extracted and ground-measured PH (R2 = 0.89, RMSE=5.08 cm). Furthermore, VIs, PH and CC exhibit strong correlations with AGB during the mid-tillering to flowering stages. The optimal AGB estimation results during the mid-tillering to flowering stages on plot data were from the PLSR model with VIs and DAT as inputs (R 2 = 0.88, RMSE=1111kg/ha, NRMSE=9.76%), and with VIs, PH, CC, and DAT all as inputs (R 2 = 0.88, RMSE=1131 kg/ha, NRMSE=9.94%). For the field sampling data, the ENet model combined with different feature inputs had the best estimation results (%error=0.6%-13.5%), demonstrating excellent practical applicability. Discussion: Model evaluation and feature importance ranking demonstrated that augmenting VIs with temporal and spatial parameters significantly enhanced the AGB estimation accuracy. In summary, the fusion of spectral and spatio-temporal features enhanced the actual physical significance of the AGB estimation models and showed great potential for accurate rice AGB estimation during the main phenological stages.

Genetically predicted systemic inflammation and the risk of atrial fibrillation: A bidirectional two-sample Mendelian randomization study.

Background: Systemic inflammation has been proposed to be associated with the incidence of atrial fibrillation (AF), but whether it is a cause or a consequence of AF remains uncertain. We sought to explore the causal associations between systemic inflammation and AF using bidirectional Mendelian randomization (MR) analysis. Methods: Independent genetic variants strongly associated with AF were selected as instrumental variables from the largest genome-wide association study (GWAS) with up to 1,030,836 individuals. Regarding inflammation traits, genetic associations with 41 inflammatory cytokines and 5 inflammatory biomarkers were obtained from their corresponding GWASs databases. Effect estimates were primarily evaluated using the inverse-variance weighted (IVW) method, supplemented by sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO methods. Results: In our initial MR analyses, we observed suggestive associations of genetically predicted interleukin-17 (IL-17), interleukin-2 receptor subunit alpha (IL-2rα), and procalcitonin (PCT) with AF. One standard deviation (SD) increase in IL-17, IL-2rα, and PCT caused an increase in AF risk by 6.3 % (OR 1.063, 95 %CI 1.011---1.118, p = 0.018), 4.9 % (OR 1.049, 95 %CI 1.007---1.094, p = 0.023) and 3.4 % (OR 1.034, 95 %CI 1.005---1.064, p = 0.022), respectively. Furthermore, our reverse MR analyses indicated that genetically predicted AF contributed to a suggestive increase in the levels of macrophage inflammatory protein-1ß (MIP1ß) (ß 0.055, 95 %CI 0.006 to 0.103, p = 0.028), while a decrease in the levels of fibrinogen (Fbg) (ß -0.091, 95 %CI -0.140 to -0.041, p < 0.001), which remained significant after multiple test correction. Conclusions: Our MR study identified several inflammatory biomarkers with suggestive causal associations regarding the upstream and downstream regulation of AF occurrence, offering new insights for therapeutic exploitation of AF. Further research is required to validate the underlying link between systemic inflammation and AF in larger cohorts.

The Relationship Between Temporal Sense and Psychopathologies of College Students with Sensory Impairments: Mediation of Religions.

Previous studies on the relationship between temporal sense and negative mental health symptoms have focused primarily on healthy college students, overlooking the role of religion. This study sought to examine the impact of religion on college students with sensory impairment and fill a gap in the research on the relationship between temporal sense and negative mental health symptoms in this population. The results were obtained from a cross sectional survey of 540 participants, including 370 hearing-impaired students and 140 visually impaired students. The survey investigated the mediating effect of religion on the relationship between temporal sense and negative mental health symptoms in impaired students. The rates of negative mental health symptoms (depression, anxiety, and stress) detected were 18.9%, 31.1%, and 2.9%, respectively. Students with different types of sensory impairments showed significant differences in their perception of time. The percentages of students with sensory impairments who attended church and practiced religion were 2.0%, 6.0%, and 1.0%, respectively. The results revealed a significant positive correlation between temporal sense and negative mental health symptoms, with religion serving as a mediating factor.

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis.

BACKGROUND: Both N6-methyladenosine (m6A) methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis (UC). However, a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed. AIM: To elucidate the autophagy-related genes of m6A with a diagnostic value for UC. METHODS: The correlation between m6A-related genes and autophagy-related genes (ARGs) was analyzed. Finally, gene set enrichment analysis (GSEA) was performed on the characteristic genes. Additionally, the expression levels of four characteristic genes were verified in dextran sulfate sodium (DSS)-induced colitis in mice. RESULTS: GSEA indicated that BAG3, P4HB and TP53INP2 were involved in the inflammatory response and TNF-α signalling via nuclear factor kappa-B. Furthermore, polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group. CONCLUSION: This study identified four m6A-ARGs that predict the occurrence of UC, thus providing a scientific reference for further studies on the pathogenesis of UC.

Metal-Organic Frameworks-Derived Nanocarbon Materials and Nanometal Oxides for Photocatalytic Applications.

Harnessing low-density solar energy and converting it into high-density chemical energy through photocatalysis has emerged as a promising avenue for the production of chemicals and remediation of environmental pollution, which contributes to alleviating the overreliance on fossil fuels. In recent years, metal-organic frameworks (MOFs) have gained widespread application in the field of photocatalysis due to their photostability, tunable structures, and responsiveness in the visible light range. However, most MOFs exhibit relatively low response to light, limiting their practical applications. MOFs-derived nanomaterials not only retain the inherent advantages of pristine MOFs but also show enhanced light adsorption and responsiveness. This review categorizes and summarizes MOFs-derived nanomaterials, including nanocarbons and nanometal oxides, providing representative examples for the synthetic strategies of each category. Subsequently, the recent research progress on MOFs-derived materials in photocatalytic applications are systematically introduced, specifically in the areas of photocatalytic water splitting to H2, photocatalytic CO2 reduction, and photocatalytic water treatment. The corresponding mechanisms involved in each photocatalytic reaction are elaborated in detail. Finally, the review discusses the challenges and further directions faced by MOFs-derived nanomaterials in the field of photocatalysis, highlighting their potential role in advancing sustainable energy production and environmental remediation.

Inorganic Halide Perovskite Nanowires/Conjugated Polymer Heterojunction-Based Optoelectronic Synaptic Transistors for Dynamic Machine Vision.

Inspired by the retina, artificial optoelectronic synapses have groundbreaking potential for machine vision. The field-effect transistor is a crucial platform for optoelectronic synapses that is highly sensitive to external stimuli and can modulate conductivity. On the basis of the decent optical absorption, perovskite materials have been widely employed for constructing optoelectronic synaptic transistors. However, the reported optoelectronic synaptic transistors focus on the static processing of independent stimuli at different moments, while the natural visual information consists of temporal signals. Here, we report CsPbBrI2 nanowire-based optoelectronic synaptic transistors to study the dynamic responses of artificial synaptic transistors to time-varying visual information for the first time. Moreover, on the basis of the dynamic synaptic behavior, a hardware system with an accuracy of 85% is built to the trajectory of moving objects. This work offers a new way to develop artificial optoelectronic synapses for the construction of dynamic machine vision systems.

Facile fabrication of a novel, photodetachable salecan-based hydrogel dressing with self-healing, injectable, and antibacterial properties based on metal coordination.

Achieving the controllable detachment of polysaccharide-based wound dressings is challenging. In this study, a novel, photodetachable salecan-based hydrogel dressing with injectable, self-healing, antibacterial, and wound healing properties was developed using a green and facile approach. A salecan hydrogel with a uniform porous structure and water content of 90.4 % was prepared by simply mixing salecan and an Fe3+-citric acid complexing solution in an acidic D-(+)-glucono-1,5-lactone environment. Metal coordinate interactions were formed between the released Fe3+ ions and carboxyl groups on the salecan polysaccharide, inducing homogeneous gelation. Benefiting from this dynamic and reversible crosslinking, the salecan hydrogel exhibited self-healing and injectable behavior, facilitating the formation of the desired shapes in situ. The exposure of Fe3+-citric acid to UV light (365 nm) resulted in the reduction of Fe3+ to Fe2+ through photochemical reactions, enabling phototriggered detachment. Moreover, the hydrogel exhibited excellent biocompatibility and satisfactory antibacterial efficacy against Escherichia coli and Staphylococcus aureus of 72.5 % and 85.3 %, respectively. The adhesive strength of the salecan hydrogel to porcine skin was 1.06 ± 0.12 kPa. In vivo wound healing experiments further highlighted the advantages of the prepared hydrogel in alleviating the degree of wound inflammation and promoting tissue regeneration within 12 days.

Comparison of gamithromycin residue depletion in yellow-feather and white-feather broilers after one single subcutaneous injection.

This study aimed to compare the residue depletion of gamithromycin in yellow-feather and white-feather broilers, using Sanhuang and Arbor Acres chickens as typical examples, respectively. Each breed (54 chickens) received a single subcutaneous dose of gamithromycin at 7.5 mg/kg bodyweight (BW). Tissues, including muscle, skin + fat, liver, kidney, and injection site, were collected at 6 h, 3, 5, 7, 10, 14, 21, 28, and 35 d postdrug administration. Gamithromycin concentrations in these tissues were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The kinetics of gamithromycin were analyzed in different tissues using a noncompartmental method in the Phoenix software. Differences were observed in gamithromycin concentrations and kinetic characteristics in both breeds of chickens, with higher residue concentrations and longer residue times found in yellow-feathered broilers. In Sanhuang broilers, the elimination rates of gamithromycin followed this order: injection site > muscle > liver > kidney > skin + fat. The corresponding elimination half-lives (t1/2λzs) in these samples were 1.22, 1.30, 1.71, 2.04, and 2.52 d, respectively. In contrast, in Arbor Acres broilers, a different order was noted: muscle > injection site > kidney > liver > skin + fat, with corresponding t1/2λzs of 1, 1.23, 1.88, 1.93, and 2.21 d, respectively. These differences may be related to variations in pigments in various tissues of chickens of the 2 breeds. However, further investigations are warranted to discern the underlying reasons.

CMR feature tracking-based left atrial mechanics predicts response to cardiac resynchronization therapy and adverse outcomes.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for advanced heart failure (HF) with prolonged QRS duration. However, 30% of patients have shown no benefit from the treatment. OBJECTIVE: This study aimed to examine the value of left atrial (LA) mechanics by cardiac magnetic resonance (CMR) to predict response to CRT and clinical outcomes. METHODS: A total of 163 CRT recipients with preimplantation CMR examination were retrospectively recruited. CMR feature tracking was used to evaluate LA size and function. The end points include (1) improvement of at least 5% in left ventricular ejection fraction combined with a reduction of at least 1 New York Heart Association functional class at 6-month follow-up and (2) any all-cause death or HF hospitalization during follow-up. RESULTS: Overall, 82 (50.3%) were CRT responders. CRT nonresponders had larger LA and worse LA reservoir and booster pump function than did responders (P < .001 for all). LA structural (maximum volume index < 47 mL/m2) and functional (booster pump strain > 8.5%) criteria were incremental to traditional indicators in detecting CRT response (χ2, 40.83 vs 9.98; P < .001). During follow-up (median 41 months), survival free from death or HF hospitalization increased with the number of positive LA criteria (log-rank, P < .001). After adjustment for clinical confounders, the absence of the 2 criteria remained associated with a considerably increased risk of death or HF hospitalization (adjusted hazard ratio 6.2; 95% confidence interval 2.15-17.88; P = .001). CONCLUSION: The preprocedure LA mechanics evaluated using CMR may be useful to predict response to CRT and improve risk stratification in CRT recipients.

Development and Validation of a Novel Predictive Model for the Early Differentiation of Cardiac and Non-Cardiac Syncope.

Background: The diagnosis of cardiac syncope remains a challenge. This study sought to develop and validate a diagnostic model for the early identification of individuals likely to have a cardiac cause. Methods: 877 syncope patients with a determined cause were retrospectively enrolled at a tertiary heart center. They were randomly divided into the training set and validation set at a 7:3 ratio. We analyzed the demographic information, medical history, laboratory tests, electrocardiogram, and echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. Then a multivariable logistic regression analysis was performed to identify independent predictors and construct a diagnostic model. The receiver operating characteristic curves, area under the curve (AUC), calibration curves, and decision curve analysis were used to evaluate the predictive accuracy and clinical value of this nomogram. Results: Five independent predictors for cardiac syncope were selected: BMI (OR 1.088; 95% CI 1.022-1.158; P =0.008), chest symptoms preceding syncope (OR 5.251; 95% CI 3.326-8.288; P <0.001), logarithmic NT-proBNP (OR 1.463; 95% CI 1.240-1.727; P <0.001), left ventricular ejection fraction (OR 0.940; 95% CI 0.908-0.973; P <0.001), and abnormal electrocardiogram (OR 6.171; 95% CI 3.966-9.600; P <0.001). Subsequently, a nomogram based on a multivariate logistic regression model was developed and validated, yielding AUC of 0.873 (95% CI 0.845-0.902) and 0.856 (95% CI 0.809-0.903), respectively. The calibration curves showcased the nomogram's reasonable calibration, and the decision curve analysis demonstrated good clinical utility. Conclusion: A diagnostic tool providing individualized probability predictions for cardiac syncope was developed and validated, which may potentially serve as an effective tool to facilitate early identification of such patients.

DKK1 activates the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and regulates Wnt3a-induced MSC migration.

Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where DKK1, an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 ng/ml to 100 ng/ml, while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/ml). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified CKAP4, another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway, and found that CKAP4-P/A suppressed DKK1 (100 ng/ml)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/ml) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathway in this process.

In vitro antibacterial activity of danofloxacin against Escherichia coli in Gushi chickens and its residue depletion following multiple oral administration.

This study aimed to investigate the in vitro antibacterial activity of danofloxacin against Escherichia coli isolated from Gushi chickens, as well as the tissue distribution and residue depletion of danofloxacin in Gushi chickens following multiple oral administration. A total of 42 clinical E. coli strains were isolated from the cloaca of locally farmed Gushi chickens between August and October 2023. Then the minimum inhibitory concentration (MIC) of danofloxacin against these isolates was determined by broth microdilution method. Additionally, 42 healthy Gushi chickens were randomly divided into 6 groups, and danofloxacin was orally administered at a dose of 5 mg/kg body weight (BW) for 3 consecutive days. Plasma, intestinal content, and tissue samples, including muscle, skin + fat, liver, kidney, lung, and intestine, were collected at 4, 12, 24, 48, 72, and 120 h after the last administration. Danofloxacin concentrations in all samples were determined using a high-performance liquid chromatography (HPLC) method. The average concentration vs. time data were then subjected to noncompartmental analysis using Phoenix software, and withdrawal periods for danofloxacin in Gushi chickens were further determined with WT1.4 software, setting a 95% confidence interval. Results indicated a notable inhibitory effect of danofloxacin on E. coli, with an MIC50 of 0.5 µg/mL. Additionally, danofloxacin exhibited widespread distribution in Gushi chickens, detectable in all collected samples. Among all tissues, the liver exhibited the highest concentration, followed by the intestine. Even on the fifth day postadministration, danofloxacin persisted in skin + fat, liver, and lung. The elimination half-lives (t1/2λzs) of danofloxacin varied across samples: skin + fat (47.87 h), lung (30.61 h), liver (22.07 h), plasma (16.05 h), muscle (12.53 h), intestine (9.83 h), and kidney (6.34 h). Considering residue depletion and the maximum residue limit (MRL) of danofloxacin in poultry set by Chinese regulatory authorities, withdrawal periods for the kidney, muscle, liver, and skin + fat were determined as 1.03, 1.38, 3.34, and 5.85 d, respectively, rounded to a final withdrawal time of 6 d.

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.

BACKGROUND: Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies. METHODS: In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer. RESULTS: Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging. CONCLUSION: CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

T cell-mediated skin-brain axis: Bridging the gap between psoriasis and psychiatric comorbidities.

Psoriasis, a chronic inflammatory skin condition, is often accompanied by psychiatric comorbidities such as anxiety, depression, suicidal ideation, and other mental disorders. Psychological disorders may also play a role in the development and progression of psoriasis. The intricate interplay between the skin diseases and the psychiatric comorbidities is mediated by the 'skin-brain axis'. Understanding the mechanisms underlying psoriasis and psychiatric comorbidities can help improve the efficacy of treatment by breaking the vicious cycle of diseases. T cells and related cytokines play a key role in the pathogenesis of psoriasis and psychiatric diseases, and are crucial components of the 'skin-brain axis'. Apart from damaging the blood-brain barrier (BBB) directly, T cells and secreted cytokines could interact with the hypothalamic-pituitary-adrenal axis (HPA axis) and the sympathetic nervous system (SNS) to exacerbate skin diseases or mental disorders. However, few reviews have systematically summarized the roles and mechanisms of T cells in the interaction between psoriasis and psychiatric comorbidities. In this review, we discussed several key T cells and their roles in the 'skin-brain axis', with a focus on the mechanisms underlying the interplay between psoriasis and mental commodities, to provide data that might help develop effective strategies for the treatment of both psoriasis and psychiatric comorbidities.

Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications.

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau, China relies on discovering new plant fossils. The Qaidam Basin has long been regarded as an ideal 'field laboratory' to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau. However, fossil angiosperms from the Qaidam Basin are rare, and our knowledge of its paleovegetation is poor. Here, we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin (Huatugou area). Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis. These findings, together with other reported fossil plants from the same locality, reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene. The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene. This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies, which transported moisture and provided favorable climatic conditions. Indeed, fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest, which differs from the region's modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

[Reconstitution of the in vitro STUB1-mediated ubiquitination reaction system for α-1 antitrypsin mutant Z protein].

The α-1 antitrypsin Z-mutant protein (ATZ) is the primary cause of α-1 antitrypsin deficiency (AATD). Studying the ubiquitination modification and degradation of ATZ protein is importance for developing treatments for AATD. STUB1 is an important E3 ubiquitin ligase that regulates ubiquitination modification of various proteins. However, whether STUB1 in involved in the ubiquitination modification of ATZ has not been fully elucidated. In this study, the ATZ and STUB1 coding genes were first cloned into the pET28a plasmid, constructing 2 protein expression plasmids. The recombinant plasmids were then transferred into the Escherichia coli for expression. With the optimization of induction temperature and IPTG dosage, the recombinant proteins were successfully expressed. The target proteins were then efficiently purified from cell lysates using metal-chelating affinity chromatography, and the accuracy of the amino acid sequence was verified through protein mass spectrometry analysis. Using the purified ATZ and STUB1, we established an in vitro ubiquitination reaction system. Experimental results showed that, in the presence of ATP, E1 ubiquitin-activating enzyme, and E2 ubiquitin-conjugating enzyme, STUB1 catalyzed the ubiquitination modification of ATZ. This study provides a method for obtaining the ATZ protein in vitro, elucidates the mechanism of STUB1 mediating ATZ ubiquitination, thereby advancing our understanding of the intracellular degradation mechanism of the α-1 antitrypsin Z-mutant.

Maresins as novel anti-inflammatory actors and putative therapeutic targets in sepsis.

Sepsis, a complex clinical syndrome characterized by an exaggerated host response to infection, often necessitates hospitalization and intensive care unit admission. Delayed or inaccurate diagnosis of sepsis, coupled with suboptimal treatment strategies, can result in unfavorable outcomes, including mortality. Maresins, a newly discovered family of lipid mediators synthesized from docosahexaenoic acid by macrophages, have emerged as key players in promoting inflammation resolution and the termination of inflammatory processes. Extensive evidence has unequivocally demonstrated the beneficial effects of maresins in modulating the inflammatory response associated with sepsis; however, their bioactivity and functions exhibit remarkable diversity and complexity. This article presents a comprehensive review of recent research on the role of maresins in sepsis, aiming to enhance our understanding of their effectiveness and elucidate the specific mechanisms underlying their actions in sepsis treatment. Furthermore, emerging insights into the management of patients with sepsis are also highlighted.

Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further. METHODS: We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell-cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC. RESULTS: The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC. CONCLUSIONS: The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.