High-Performance W-Doped Bi0.5Sb1.5Te3 Flexible Thermoelectric Films and Generators.

Bi-Sb-Te-based thermoelectric materials have the best room-temperature thermoelectric properties, but their inherent brittleness and rigidity limit their application in the wearable field. In this study, W-doped p-type Bi0.5Sb1.5Te3 (W-BST) thin films were prepared using magnetron sputtering on polyimide substrates to create thermoelectric generators (TEGs). Bending tests showed that the thin film has excellent flexibility and mechanical durability, meeting the flexible requirements of wearable devices. W doping can significantly increase the carrier concentration, Seebeck coefficient, and electrical conductivity of BST thin films. At 300 K, the power factor of the W-BST film is 2.25 times higher than that of the undoped film, reaching 13.75 µW cm-1 K-2. First-principles calculations showed that W doping introduces significant impurity peaks in the bandgap, in which W d electrons remarkably hybridize with the Sb and Te p electrons, leading to an improved electrical conductivity of BST films. Furthermore, W doping significantly reduces the work function of BST films, thereby improving the carrier mobility. A TEG module fabricated from four layers of W-BST thin films achieved a maximum output power density of 6.91 mW cm-2 at a temperature difference of 60 K. Application tests showed that the flexible TEG module could power a portable clock using the temperature difference between body temperature and room temperature. At a medium temperature of 439 K, the assembled TEG module can provide a stable output voltage of 1.51 V to power a LED. This study demonstrates the feasibility of combining inorganic thermoelectric materials with flexible substrates to create high-performance flexible TEGs.

Activation of the Nrf2/ARE signaling pathway ameliorates hyperlipidemia-induced renal tubular epithelial cell injury by inhibiting mtROS-mediated NLRP3 inflammasome activation.

Dyslipidemia is the most prevalent independent risk factor for patients with chronic kidney disease (CKD). Lipid-induced NLRP3 inflammasome activation in kidney-resident cells exacerbates renal injury by causing sterile inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that modulates the cellular redox balance; however, the exact role of Nrf2 signaling and its regulation of the NLRP3 inflammasome in hyperlipidemia-induced kidney injury are poorly understood. In this study, we demonstrated that activation of the mtROS-NLRP3 inflammasome pathway is a critical contributor to renal tubular epithelial cell (RTEC) apoptosis under hyperlipidemia. In addition, the Nrf2/ARE signaling pathway is activated in renal tubular epithelial cells under hyperlipidemia conditions both in vivo and in vitro, and Nrf2 silencing accelerated palmitic acid (PA)-induced mtROS production, mitochondrial injury, and NLRP3 inflammasome activation. However, the activation of Nrf2 with tBHQ ameliorated mtROS production, mitochondrial injury, NLRP3 inflammasome activation, and cell apoptosis in PA-induced HK-2 cells and in the kidneys of HFD-induced obese rats. Furthermore, mechanistic studies showed that the potential mechanism of Nrf2-induced NLRP3 inflammasome inhibition involved reducing mtROS generation. Taken together, our results demonstrate that the Nrf2/ARE signaling pathway attenuates hyperlipidemia-induced renal injury through its antioxidative and anti-inflammatory effects through the downregulation of mtROS-mediated NLRP3 inflammasome activation.

The disease recurrence perception scale for patients with inflammatory bowel disease: Instrument development and cross-sectional validation study.

Disease recurrence perception plays a key role in disease management and subsequent disease recurrence prevention. However, there are no specific tools for assessing disease recurrence perception in patients with inflammatory bowel disease (IBD) characterized by alternating remission and recurrence. To develop and validate an instrument for measuring disease recurrence perception of patients with IBD, the study was conducted in two steps: (1) instrument development and (2) psychometric tests. A total of 623 patients with IBD participated in the study. The common sense model of illness self-regulation (CSM) was used as a framework for instrument development. The administered version contained 48 items intended to be relevant to at least one of the six dimensions of the model. Based on preliminary analyzes, 12 items were deleted leaving 36 items for more detailed psychometric and factor analyzes. The Cronbach's alpha coefficient of the total 36-item instrument was 0.915. The content validity indexes at item and scale levels were satisfactory. The test-retest reliability of the total instrument was 0.870. Exploratory principal components analysis (n = 278) was used to identify six components congruent with intended CSM constructs that accounted for 62.6% of total item variance. Confirmatory factor analysis (n = 345) found acceptable fit for the six factor measurement model (χ2/df = 1.999, GFI = 0.846, NFI = 0.855, IFI = 0.922, TLI = 0.910, CFI = 0.921, RMSEA = 0.054). Overall, the DRPSIBD demonstrated satisfactory reliability and validity to warrant further development as a measure of disease recurrence perception of patients with IBD.

Role of endothelial Raptor in abnormal arteriogenesis after lower limb ischemia in type-2 diabetes.

AIMS: Proper arteriogenesis after tissue ischemia is necessary to rebuild stable blood circulation; nevertheless, this process is impaired in type-2 diabetes mellitus (T2DM). Raptor, is a scaffold protein and a component of mammalian target of rapamycin complex 1 (mTORC1). However, the role of the endothelial Raptor in arteriogenesis under the conditions of T2DM remains unknown. This study investigated the role of endothelial Raptor in ischemia-induced arteriogenesis during T2DM. METHODS AND RESULTS: Although endothelial mTORC1 is hyperactive in T2DM, we observed a marked reduction in the expression of endothelial Raptor in two mouse models and in human vessels. Inducible endothelial-specific Raptor knockout severely exacerbated impaired hindlimb perfusion and arteriogenesis after hindlimb ischemic injury in 12-week high-fat diet fed mice. Additionally, we found that Raptor deficiency dampened vascular endothelial growth factor receptor 2 (VEGFR2) signaling in endothelial cells and inhibited VEGF-induced cell migration and tube formation in a PTP1B-dependent manner. Furthermore, mass spectrometry analysis indicated that Raptor interacts with neuropilin 1 (NRP1), the co-receptor of VEGFR2, and mediates VEGFR2 trafficking by facilitating the interaction between NRP1 and Synectin. Finally, we found that endothelial cell-specific overexpression of the Raptor mutant (loss of mTOR binding) reversed impaired hindlimb perfusion and arteriogenesis induced by endothelial Raptor knockout in high-fat diet fed mice. CONCLUSIONS: Collectively, our study demonstrated the crucial role of endothelial Raptor in promoting ischemia-induced arteriogenesis in T2DM by mediating VEGFR2 signaling. Thus, endothelial Raptor is a novel therapeutic target for promoting arteriogenesis and ameliorating perfusion in T2DM.

What can we learn when fitting a simple telegraph model to a complex gene expression model?

In experiments, the distributions of mRNA or protein numbers in single cells are often fitted to the random telegraph model which includes synthesis and decay of mRNA or protein, and switching of the gene between active and inactive states. While commonly used, this model does not describe how fluctuations are influenced by crucial biological mechanisms such as feedback regulation, non-exponential gene inactivation durations, and multiple gene activation pathways. Here we investigate the dynamical properties of four relatively complex gene expression models by fitting their steady-state mRNA or protein number distributions to the simple telegraph model. We show that despite the underlying complex biological mechanisms, the telegraph model with three effective parameters can accurately capture the steady-state gene product distributions, as well as the conditional distributions in the active gene state, of the complex models. Some effective parameters are reliable and can reflect realistic dynamic behaviors of the complex models, while others may deviate significantly from their real values in the complex models. The effective parameters can also be applied to characterize the capability for a complex model to exhibit multimodality. Using additional information such as single-cell data at multiple time points, we provide an effective method of distinguishing the complex models from the telegraph model. Furthermore, using measurements under varying experimental conditions, we show that fitting the mRNA or protein number distributions to the telegraph model may even reveal the underlying gene regulation mechanisms of the complex models. The effectiveness of these methods is confirmed by analysis of single-cell data for E. coli and mammalian cells. All these results are robust with respect to cooperative transcriptional regulation and extrinsic noise. In particular, we find that faster relaxation speed to the steady state results in more precise parameter inference under large extrinsic noise.

Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome.

Cytokine storm syndrome (CSS) is a life-threatening systemic inflammatory syndrome involving innate immune hyperactivity triggered by various therapies, infections, and autoimmune conditions. However, the potential interplay between innate immune cells is not fully understood. Here, using poly I:C and lipopolysaccharide (LPS)-induced cytokine storm models, a protective role of neutrophils through the modulation of macrophage activation was identified in a CSS model. Intravital imaging revealed neutrophil-derived extracellular vesicles (NDEVs) in the liver and spleen, which were captured by macrophages. NDEVs suppressed proinflammatory cytokine production by macrophages when cocultured in vitro or infused into CSS models. Metabolic profiling of macrophages treated with NDEV revealed elevated levels of the anti-inflammatory metabolite, itaconate, which is produced from cis-aconitate in the Krebs cycle by cis-aconitate decarboxylase (Acod1, encoded by Irg1). Irg1 in macrophages, but not in neutrophils, was critical for the NDEV-mediated anti-inflammatory effects. Mechanistically, NDEVs delivered miR-27a-3p, which suppressed the expression of Suclg1, the gene encoding the enzyme that metabolizes itaconate, thereby resulting in the accumulation of itaconate in macrophages. These findings demonstrated that neutrophil-to-macrophage communication mediated by extracellular vesicles is critical for promoting the anti-inflammatory reprogramming of macrophages in CSS and may have potential implications for the treatment of this fatal condition.

Reconstructing Kaolinite Compounds for Remarkably Enhanced Adsorption of Congo Red.

Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.

Circulating tumor cells: a valuable indicator for locally advanced nasopharyngeal carcinoma.

BACKGROUND: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. METHODS: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. RESULTS: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. CONCLUSION: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.

Assessment of fish protein hydrolysate as a substitute for fish meal in white shrimp diets: Impact on growth, immune response, and resistance against Vibrio parahaemolyticus infection.

This study investigated the effects of fish protein hydrolysate derived from barramundi on growth performance, muscle composition, immune response, disease resistance, histology and gene expression in white shrimp (Penaeus vannamei). In vitro studies demonstrated FPH enhanced mRNA expressions of key immune-related genes and stimulated reactive oxygen species (ROS) production and phagocytic activity in shrimp hemocytes. To evaluate the effects of substituting fish meal with FPH in vivo, four isoproteic (43 %), isolipidic (6 %), and isoenergetic diets (489 kcal/100 g) were formulated with fish meal substitution levels of 0 % (control), 30 % (FPH30), 65 % (FPH65), and 100 % (FPH100). After 8-week feeding, the growth performance of FPH65 and FPH100 were significantly lower than that of control and FPH30 (p < 0.05). Similarly, the midgut histological examination revealed the wall thickness and villi height of FPH100 were significantly lower than those of control (p < 0.05). The shrimps were received the challenge of AHPND + Vibrio parahaemolyticus at week 4 and 8. All FPH-fed groups significantly enhanced resistance against Vibrio parahaemolyticus at week 4 (p < 0.05). However, this protective effect diminished after long-period feeding. No significant difference of survival rate was observed among all groups at week 8 (p > 0.05). The expressions of immune-related genes were analyzed at week 4 before and after challenge. In control group, V. parahaemolyticus significantly elevated SOD in hepatopancreas and Muc 19, trypsin, Midline-fas, and GPx in foregut (p < 0.05). Moreover, hepatopancreatic SOD of FPH65 and FPH100 were significantly higher than that of control before challenge (p < 0.05). Immune parameters were measured at week 8. Compared with control, the phagocytic index of FPH 30 was significantly higher (p < 0.05). However, dietary FPH did not alter ROS production, phenoloxidase activity, phagocytic rate, and total hemocyte count (p > 0.05). These findings suggest that FPH30 holds promise as a feed without adverse impacts on growth performance while enhancing the immunological response of white shrimp.

Recurrence Characteristics on Optical Coherence Tomography and Treatments of Reis-Bücklers Corneal Dystrophy after Phototherapeutic Keratectomy or Penetrating Keratoplasty: Recurrence characteristics and treatments of RBCD.

PURPOSE: To evaluate the recurrence characteristics on optical coherence tomography and clinical outcomes after phototherapeutic keratectomy (PTK) or penetrating keratoplasty (PKP) in patients with Reis-Bücklers corneal dystrophy (RBCD). DESIGN: Retrospective interventional case series. METHODS: Seventeen patients with RBCD (31 eyes, including six surgery-naïve eyes and 25 surgical eyes) received 44 surgical interventions from 1996 through 2022. PTK or PKP was performed as the initial surgical procedure. Significant recurrence was determined when best spectacle-corrected visual acuity decreased at least two lines with increased opacity in the superficial cornea. Repeated PTK or PTK on the corneal graft (CG-PTK) was considered if patients could not endure poor vision due to significant recurrence. Recurrence depth and annual increase in thickness of the central cornea and subepithelial deposits were assessed by anterior segment optical coherence tomography. RESULTS: The mean follow-up time was 12.8±8.5 years (range, 2.0-25.5 years). The mean logMAR best spectacle-corrected visual acuity improved from 1.24±0.48 preoperatively to 0.27±0.09 postoperatively in the initial PTK group (13 eyes, P<0.001), from 1.84±0.69 to 0.40±0.13 in the PKP group (12 eyes, P<0.001), from 1.04±0.46 to 0.30±0.07 in the repeated PTK group (12 times in 7 eyes, P<0.001), and from 1.29±0.43 to 0.39±0.11 in the CG-PTK group (7 times in 5 eyes, P=0.001). The median significant recurrence time was 27 months (95% confidence interval 23.9-30.1), 96 months (84.1-107.9), 31 months (28.8-33.1), and 24 months (19.8-28.2), respectively (P<0.001). The depth of superficial deposits located between the epithelium and the anterior stroma was approximately 115µm (85-159µm). The annual thickening of subepithelial deposits was 14±2µm after initial PTK, 7±3µm after PKP, 14±3µm after repeated PTK, and 30±11µm after CG-PTK, compared to 4±2µm in surgery-naïve eyes (P=0.002, 0.515, 0.002, <0.001). The thickness of the central cornea increased by 15±2µm, 7±2µm, 15±3µm, and 31±10µm per year in the four surgery groups, respectively, compared to 5±2µm in surgery-naïve eyes (P=0.001, 0.469, 0.001, <0.001). CONCLUSIONS: Better visual acuity can be achieved after PTK than PKP for treatment of RBCD. The annual thickening of subepithelial deposits may approximate an increase in central corneal thickness. The superficial distribution of subepithelial deposits makes it feasible to perform repeated PTK, even on the corneal allograft, for recurrent RBCD.

Prognostic value of sarcopenia in the patients with locally advanced nasopharyngeal carcinoma.

PURPOSE: Sarcopenia, characterized by loss of muscle mass index (SMI), serves as a diagnostic indicator for malnutrition and has been shown to influence cancer treatment outcomes. The objective of this study was to investigate the prognostic significance of sarcopenia on the locally advanced nasopharyngeal carcinoma (laNPC) patients. PATIENTS AND METHODS: 545 patients with stage III-IVa NPC were included in this retrospective study. Sarcopenia was defined using the skeletal muscle index (SMI) determined at the C3 level based on baseline MRI. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: The results of the multivariate analysis revealed that sarcopenia group (HR = 2.82, 95% CI 1.96-4.06, P < 0.01), T4 stage (HR = 1.64, 95% CI 1.24-2.15, P < 0.01), N3 stage (HR = 1.91, 95% CI 1.52-2.40, P < 0.01), comorbidities (HR = 2.08, 95% CI 1.45-2.97, P < 0.01), and any adverse event grade 3-4 (HR = 1.48, 95% CI 1.04-2.01, P = 0.03) were identified as independent risk factors that significantly impacted the OS. Additionally, sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), T4 stage (HR = 1.50, 95% CI 1.17-1.92, P < 0.01), N3 stage (HR = 1.80, 95% CI 1.46-2.22, P < 0.01), sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), and any adverse event grade 3-4 (HR = 1.45, 95% CI 1.04-2.01, P = 0.03) were found to have a significant impact on PFS. CONCLUSION: Sarcopenia was identified as a prognostic factor for patients with laNPC. Furthermore, T stage, N stage, comorbidities, and any adverse event grade 3-4 were identified as independent prognostic factors for laNPC.

Synergistic effect of Ti3C2Tx MXene/PAN nanofiber and LLZTO particles on high-performance PEO-based solid electrolyte for lithium metal battery.

Solid polymer electrolytes (SPEs) have been considered the most promising separators for all-solid-state lithium metal batteries (ASSLMBs) due to their ease of processing and low cost. However, the practical applications of SPEs in ASSLMBs are limited by their low ionic conductivities and mechanical strength. Herein, we developed a three-dimensional (3D) interconnected MXene (Ti3C2Tx) network and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) particles synergistically reinforced polyethylene oxide (PEO)-based SPE, where the association of Li+ with ether-oxygen in PEO could be significantly weakened through the Lewis acid-base interactions between the electron-absorbing group (Ti-F, -O-) of Ti3C2Tx and Li+. Besides, the TFSI- in lithium salts could be immobilized by hydrogen bonds from the Ti-OH of Ti3C2Tx. The 3D interconnected Ti3C2Tx network not only alleviated the agglomeration of inorganic fillers (LLZTO), but also improved the mechanical strength of composite solid electrolyte (CSE). Consequently, the assembled Li||CSE||Li symmetric battery showed excellent cycling stability at 35 ℃ (stable cycling over 3000 h at 0.1 mA cm-2, 0.1 mAh cm-2) and -2 ℃ (stable cycling over 2500 h at 0.05 mA cm-2, 0.05 mAh cm-2). Impressively, the LiFePO4||CSE||Li battery showed a high discharge capacity of 145.3 mAh/g at 0.3 C after 300 cycles at 35 ℃. This rational structural design provided a new strategy for the preparation of high-performance solid-state electrolytes for lithium metal batteries.

Multiple polygenic risk scores can improve the prediction of systemic lupus erythematosus in Taiwan.

OBJECTIVE: To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE. METHODS: The study enrolled 2429 patients with SLE and 48 580 controls from China Medical University Hospital in Taiwan. A genome-wide association study (GWAS) and PRS analyses of SLE and other three SLE markers, namely ANA, anti-double-stranded DNA antibody (dsDNA) and anti-Smith antibody (Sm), were conducted. RESULTS: Genetic variants associated with SLE were identified through GWAS. Some novel genes, which have been previously reported, such as RCC1L and EGLN3, were revealed to be associated with SLE in Taiwan. Multiple PRS models were established, and optimal cut-off points for each PRS were determined using the Youden Index. Combining the PRSs for SLE, ANA, dsDNA and Sm yielded an area under the curve of 0.64 for the optimal cut-off points. An analysis of human leucocyte antigen (HLA) haplotypes in SLE indicated that individuals with HLA-DQA1*01:01 and HLA-DQB1*05:01 were at a higher risk of being classified into the SLE group. CONCLUSIONS: The use of PRSs to predict SLE enables the identification of high-risk patients before abnormal laboratory data were obtained or symptoms were manifested. Our findings underscore the potential of using PRSs and GWAS in identifying SLE markers, offering promise for early diagnosis and prediction of SLE.

Thermodynamic Analysis of Eplerenone in 13 Pure Solvents at Temperatures from 283.15 to 323.15 K.

The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, N,N-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, ethanol, and 1-propanol) was determined by the gravimetric method at atmospheric pressure and various temperatures (from 283.15 to 323.15 K). The results showed that the solubility of EP in the selected solvents was positively correlated with the thermodynamic temperature, and the order of solubility of EP at 298.15 K was acetonitrile > DMF > 2-butanone > methyl acetate > 4-methyl-2-pentanone > methyl propionate > ethyl acetate > propyl acetate > ethyl formate > acetone > butyl acetate > ethanol >1-propanol. The modified Apelblat model, van't Hoff model, λh model, and polynomial empirical model were used for fitting the solubility data, and then the λh model was found to have the highest fitting accuracy with a minimum ARD of 7.0 × 10-3 and a minimum RMSD of 6.1 × 10-6. The solvent effect between the solute and the solvent was analyzed using linear solvation energy relationship (LSER), and the enthalpy of solvation (ΔsolH°), entropy of solvation (ΔsolS°), and Gibbs free energy of solvation (ΔsolG°) of the dissolution process of EP were calculated by the van't Hoff model, which indicated that the dissolution process of EP in the selected solvents was endothermic, nonspontaneous, and entropy-increasing. In this work, the solubility, dissolution characteristics, and thermodynamic parameters of EP were studied, which will provide data support for the production, crystallization, and purification of EP and will provide important guidance for the crystallization optimization of EP in industry.

Mechanism of CO2 in promoting the hydrogenation of levulinic acid to γ-valerolactone catalyzed by RuCl3 in aqueous solution.

A Ru-containing complex shows good catalytic performance toward the hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) with the assistance of organic base ligands (OBLs) and CO2. Herein, we report the competitive mechanisms for the hydrogenation of LA to GVL, 4-oxopentanal (OT), and 2-methyltetrahydro-2,5-furandiol (MFD) with HCOOH or H2 as the H source catalyzed by RuCl3 in aqueous solution at the M06/def2-TZVP, 6-311++G(d,p) theoretical level. Kinetically, the hydrodehydration of LA to GVL is predominant, with OT and MFD as side products. With HCOOH as the H source, initially, the OBL (triethylamine, pyridine, or triphenylphosphine) is responsible for capturing H+ from HCOOH, leading to HCOO- and [HL]+. Next, the Ru3+ site is in charge of sieving H- from HCOO-, yielding [RuH]2+ hydride and CO2. Alternatively, with H2 as the H source, the OBL stimulates the heterolysis of H-H bond with the aid of Ru3+ active species, producing [RuH]2+ and [HL]+. Toward the [RuH]2+ formation, H2 as the H source exhibits higher activity than HCOOH as the H source in the presence of an OBL. Thereafter, H- in [RuH]2+ gets transferred to the unsaturated C site of ketone carbonyl in LA. Afterwards, the Ru3+ active species is capable of cleaving the C-OH bond in 4-hydroxyvaleric acid, yielding [RuOH]2+ hydroxide and GVL. Subsequently, CO2 promotes Ru-OH bond cleavage in [RuOH]2+, forming HCO3- and regenerating the Ru3+-active species owing to its Lewis acidity. Lastly, between the resultant HCO3- and [HL]+, a neutralization reaction occurs, generating H2O, CO2, and OBLs. Thus, the present study provides insights into the promotive roles of additives such as CO2 and OBLs in Ru-catalyzed hydrogenation.

N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression.

PURPOSE: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. METHODS: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. RESULTS: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). CONCLUSION: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low bone mineral density (BMD) (typically < -2.5 SD), cause a higher fracture risk and lead to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians. We investigated the genetic aspects of BMD in 86,716 individuals from the Taiwan Biobank and their causal links to health conditions within East Asians. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-ß. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with body mass index (BMI) and type 2 diabetes (T2D) in East Asians. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, HbA1c, and reduced T2D risk. Bidirectional Mendelian randomization (MR) analyses revealed that a higher BMI causally increases BMD in East Asians. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in East Asians, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

We investigated how genetics affect bone health and related conditions like diabetes and obesity in 86,716 East Asians. Previously, most studies focused on Caucasian populations, but our work helps to understand these issues in East Asians. Our findings show that stronger bones are linked to a lower chance of osteoporosis but a higher risk of obesity and type 2 diabetes. On the other hand, those with osteoporosis tend to have lower body weight and a decreased risk of diabetes, illustrating a complex relationship between bone health and body metabolism. Future research will focus on deeper genetic interactions and developing targeted interventions for bone health and related metabolic disorders in East Asians.

Mitochondrial genomes of four slug moths (Lepidoptera, Limacodidae): Genome description and phylogenetic implications.

The family Limacodidae belongs to the superfamily Zygaenoidea, which includes 1672 species commonly referred to as slug moths. Limacodidae larvae are major pests for many economically important plant species and can cause human dermatitis. At present, the structure of the mitochondrial genome (mitogenome), phylogenetic position, and adaptive evolution of slug moths are poorly understood. Herein, the mitogenomes of Parasa lepida, Phlossa conjuncta, Thosea sinensis, and Setora sinensis were sequenced and compared with other available mitogenome sequences to better characterize the mitogenomic diversity and evolution of this moth family. The mitogenomes of P. lepida, P. conjuncta, T. sinensis, and S. sinensis were confirmed to be circular in structure with lengths of 15,575 bp, 15,553 bp, 15,535 bp, and 15,529 bp, respectively. The Limacodidae mitogenomes exhibited similar nucleotide composition, codon usage, RNA structure, and control region patterns, indicating the conservation of the mitogenome in the family Limacodidae. A sliding window, Ka/Ks, and genetic distance analyses revealed that the atp8 and nad6 genes exhibited the highest levels of variability and the most rapid evolutionary rates among the 13 protein-coding genes (PCGs) encoded in these Limacodidae mitogenomes, suggesting that they may offer value as candidate DNA markers. The phylogenetic analysis recovered the overall relationship as Tortricoidea + (Sesiidae + (Zygaenoidea + (Cossoidea/+Choreutoidea + (others)))). Within Zygaenoidea, Limacodidae was recovered as monophyletic, and the phylogenetic relationships were recovered as (Phaudidae + Zyganidae) + Limacodidae in all six phylogenetic trees. The analysis indicated that P. lepida, P. conjuncta, T. sinensis, and S. sinensis are members of the Limacodidae.

Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Comparative Epigenetic Profiling Reveals Distinct Features of Mucosal Melanomas Associated with Immune Cell Infiltration and Their Clinical Implications.

Mucosal melanoma exhibits limited responsiveness to anti-PD-1 therapy. However, a subgroup of mucosal melanomas, particularly those situated at specific anatomical sites like primary malignant melanoma of the esophagus (PMME), display remarkable sensitivity to anti-PD-1 treatment. The underlying mechanisms driving this superior response and the DNA methylation patterns in mucosal melanoma have not been thoroughly investigated. We collected tumor samples from 50 mucosal melanoma patients, including 31 PMME and 19 non-esophageal mucosal melanoma (NEMM). Targeted bisulfite sequencing was conducted to characterize the DNA methylation landscape of mucosal melanoma and explore the epigenetic profiling differences between PMME and NEMM. Bulk RNA sequencing and multiplex immunofluorescence staining were performed to confirm the impact of methylation on gene expression and immune microenvironment. Our analysis revealed distinct epigenetic signatures that distinguish mucosal melanomas of different origins. Notably, PMME exhibited distinct epigenetic profiling characterized by a global hypermethylation alteration compared to NEMM. The prognostic model based on the methylation scores of a 7-DMR panel could effectively predict the overall survival of PMME patients and potentially serve as a prognostic factor. PMME displayed a substantial enrichment of immune-activating cells in contrast to NEMM. Furthermore, we observed hypermethylation of the TERT promoter in PMME, which correlated with heightened CD8+ T cell infiltration, and patients with hypermethylated TERT were likely to have improved responses to immunotherapy. Our results indicated that PMME shows a distinct methylation landscape compared with NEMM, and the epigenetic status of TERT might be used to estimate prognosis and direct anti-PD-1 treatment for mucosal melanoma.