Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.

BACKGROUND: Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. METHODS: We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. RESULTS: The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. CONCLUSION: This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

METTL3: Melting the tumor microenvironment for improved immunotherapy.

The tumor microenvironment (TME) dictates the outcome of cancer immunotherapy. In this issue of Cell Chemical Biology, Yu et al.1 report that targeting Mettl3 leads to a more inflamed, "hot" TME and effective anti-PD-1 therapy. This study points to a new target in remodeling the TME for improved immunotherapy.

Synergistic effect of Ag@CN with BiVO4 in a unique Z-type heterojunction for enhancing photoelectrochemical water splitting performance.

In the realm of photoelectrochemical technology, the enhancement of photogenerated charge carrier separation is pivotal for the advancement of energy conversion performance. Carbon nitride (CN) is established as a photocatalytic material with significant potential and exhibits unique advantages in addressing the issue of rapid recombination of photogenerated carriers. This study utilized an efficient in situ doping method that combined Mo,W-doped BiVO4 (Mo,W:BVO) with silver-loaded CN (Ag@CN), yielding an all-solid-state Mo,W:BVO/Ag@CN heterostructure that effectively augments the separation efficiency of electron-hole pairs. Through the annealing process, Ag@CN was uniformly coated within the Mo,W:BVO thin film, significantly enlarging the interface contact area to enhance visible light absorption and photogenerated carrier movement. The results of the photoelectrochemical tests showed that the Mo,W:BVO/Ag@CN heterostructure had the highest photocurrent and charge transfer efficiency, which were 6.4 times and 3.6 times higher respectively than those of the unmodified Mo,W:BVO. Our research elucidates the interactions within all-solid-state Z-scheme heterojunctions, outlining strategic approaches for crafting innovative and superior photocatalytic systems.

Flexible, scalable and simple-fabricated silver nanorod-decorated bacterial nanocellulose SERS substrates cooperated with portable Raman spectrometer for on-site detection of pesticide residues.

Owing to good flexibility, prominent mechanical properties, three-dimensional (3D) nanofibrous structure and low background interference, sustainable bacterial nanocellulose (BNC) is a highly attractive matrix material for surface-enhanced Raman scattering (SERS) sensor. Herein, a highly sensitive, flexible and scalable silver nanorod-decorated BNC (AgNRs@BNC) SERS sensor is developed by a simple vacuum-assisted filtration. The AgNRs were firmly locked in the 3D nanofibrous network of cellulose nanofibers upon vacuum drying process, resulting in the formation of 3D SERS hotspots with a depth of more than 10 µm on the sensor. With 4-aminothiophenol (4-ATP) as a target molecule, a lowest distinguishable level of 10-12 M and a high enhancement factor of 1.1 × 109 were realized by the optimal AgNRs1.5@BNC SERS sensor. Moreover, the AgNRs@BNC SERS sensor exhibits high detectable level of 10-9 M for thiram molecules by integrating with a portable Raman spectrometer. Besides, toxic thiram residues on grape surface could be directly on-site identified by the combination of AgNRs@BNC SERS sensors and a portable Raman spectrometer through a feasible press-and-peel method. The flexible AgNRs@BNC SERS sensor cooperated with portable Raman system demonstrates great potential for on-site detection of pesticide residues on irregular food surfaces.

Fast Prediction Method for Scattering Parameters of Rigid-Flex PCBs Based on ANN.

InGaAs detection systems have been increasingly used in the aerospace field, and due to the high signal-to-noise ratio requirements of short-wave infrared quantitative payloads, there is an urgent need for methods for the rapid and precise evaluation and the optimal design of these systems. The rigid-flex printed circuit board (PCB) is a vital component of InGaAs detectors, as its grid ground plane design parameters impact parasitic capacitance and thus affect weak infrared analog signals. To address the time-intensive and costly nature of design optimization achieved with simulations and experimental measurements, we propose an innovative method based on a neural network to predict the scattering parameters of rigid-flex boards for InGaAs detection links. This is the first study in which the effects of rigid-flex boards on weak infrared detection signals have been considered. We first obtained sufficient samples with software simulation. A backpropagation (BP) neural network prediction model was trained on existing sample sets and then verified on a rigid-flex board used in a crucial aerospace short-wave infrared quantitative mission. The model efficiently and accurately predicted high-speed interconnect scattering parameters under various rigid-flex board grid plane parameter conditions. The prediction error was less than 1% compared with a 3D field solver, indicating an overcoming of the iterative optimization inefficiency and showing improved design quality for InGaAs detection circuits.

Cryogenic Thermal Shock Effects on Optical Properties of Quantum Emitters in Hexagonal Boron Nitride.

Solid-state quantum emitters are vital building blocks for quantum information science and quantum technology. Among various types of solid-state emitters discovered to date, color centers in hexagonal boron nitride have garnered tremendous traction in recent years, thanks to their environmental robustness, high brightness, and room-temperature operation. Most recently, these quantum emitters have been employed for satellite-based quantum key distribution. One of the most important requirements to qualify these emitters for space-based applications is their optical stability against cryogenic thermal shock. Such an understanding has, however, remained elusive to date. Here, we report on the effects caused by such thermal shock that induces random, irreversible changes in the spectral characteristics of the quantum emitters. By employing a combination of structural characterizations and density functional calculations, we attribute the observed changes to lattice strain caused by cryogenic temperature shock. Our study sheds light on the stability of the quantum emitters under extreme conditions─similar to those countered in outer space.

What can we learn about stress and sleep from COVID-19 pandemic-perspective from the theory of preventive stress management.

Background: The COVID-19 pandemic has presented unique challenges to individuals worldwide, with a significant focus on the impact on sleep. However, the precise mechanisms through which emotional and cognitive variables mediate this relationship remain unclear. To expand our comprehensive understanding of variables, the present study utilizes the Preventive Stress Management theory, to test the relationship between perceived social support and sleep quality, as well as the effect of perceived COVID-19 stress, hope, negative emotions and coping styles. Methods: Data were collected in March 2022 from 1,034 college students in two universities located in Liaoning Province, China, using an online survey platform regarding perceived social support, perceived COVID-19 stress, sleep quality, hope, negative emotions and coping styles. The moderated mediation model were conducted using Process macro program (Model 6) and the syntax in SPSS. Results: The results revealed perceived COVID-19 stress and negative emotions sequentially mediated the negative relationship between perceived social support and sleep quality. Furthermore, hope and coping styles were found to moderate the sequential mediating effect. Conclusion: The present study sheds light on the pathways that affect sleep quality among college students during the COVID-19 pandemic. Findings highlight the protective roles played by positive social and personal resources, such as perceived social support, hope, and effective coping styles, against sleep problems. These insights have important implications for the development of targeted interventions to improve sleep outcomes during this challenging time.

Hematopoietic stem cell niche generation and maintenance are distinguishable by an epitranscriptomic program.

The niche is typically considered as a pre-established structure sustaining stem cells. Therefore, the regulation of its formation remains largely unexplored. Whether distinct molecular mechanisms control the establishment versus maintenance of a stem cell niche is unknown. To address this, we compared perinatal and adult bone marrow mesenchymal stromal cells (MSCs), a key component of the hematopoietic stem cell (HSC) niche. MSCs exhibited enrichment in genes mediating m6A mRNA methylation at the perinatal stage and downregulated the expression of Mettl3, the m6A methyltransferase, shortly after birth. Deletion of Mettl3 from developing MSCs but not osteoblasts led to excessive osteogenic differentiation and a severe HSC niche formation defect, which was significantly rescued by deletion of Klf2, an m6A target. In contrast, deletion of Mettl3 from MSCs postnatally did not affect HSC niche. Stem cell niche generation and maintenance thus depend on divergent molecular mechanisms, which may be exploited for regenerative medicine.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

Molecularly imprinted polymer photoelectrochemical sensor for the detection of triazophos in water based on carbon quantum dot-modified titanium dioxide.

Widely used organophosphorus pesticide triazophos (TAP) can easily cumulate in aquatic system due to its high stability chemically and photochemically and thus posing significant threat to aquatic creatures and humans' health. Urging demand for rapid determining TAP in water has risen. Photoelectrochemical (PEC) sensing turns out to be a good candidate for its simplicity in fabrication and swiftness in detection. Nevertheless, traditional PEC sensors often lack selectivity as their signal generation primarily relies on the oxidation of organic compounds in the electrolyte by photo-induced holes. To address this limitation, molecularly imprinted polymers (MIPs) can be in combined with PEC sensors to significantly enhance the selectivity. Here, we present a novel approach utilizing a PEC sensor enhanced by carbon-modified titanium dioxide molecularly imprinted polymers (MIP/C/TiO2 NTs). Carbon quantum dot (CQD) modification of titanium dioxide nanotube arrays (C/TiO2 NTs) was achieved through a one-step anodization process, effectively enhancing visible light absorption by narrowing the band gap of TiO2, and CQDs also function as sensitizer accelerating charge transfer for improved and stable photocurrent signals during detection. Our method further incorporates MIPs to heighten the selectivity of the PEC sensor. Electro-polymerization using cyclic voltammetry was employed to polymerize MIPs with pyrrole as the functional monomer and triazophos as the target molecule. The resultant MIP/C/TiO2 NT sensor exhibited remarkable sensitivity, with a detection limit of 0.03 nM (S/N = 3), alongside exceptional selectivity and stability for triazophos detection in water. This offers a promising avenue for efficient, cost-effective, and rapid monitoring of pesticide contaminants in aquatic environments, contributing to the broader goals of environmental preservation and public health.

Clinical use of macitentan in the treatment of connective tissue disease-associated pulmonary arterial hypertension.

Background: Connective tissue disease (CTD) is the second most common cause of the pulmonary arterial hypertension (PAH). Currently, clinical data concerning CTD-PAH is scarce. Our study aimed to assess the efficacy and safety of macitentan in the treatment of CTD-PAH. Methods: In this retrospective study, patients diagnosed with CTD-PAH at The First Affiliated Hospital of Soochow University from April 2020 to November 2021 were included. Of the patients, 9 were switched to macitentan monotherapy whereas 23 received initial combination therapy. The mean follow-up time was 24 weeks. Six-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography parameters before and after medication were assessed. Adverse reactions were also recorded and compared. Results: After 24 weeks of treatment, 6MWD, NT-proBNP, systolic pulmonary artery pressure (sPAP) estimated by ultrasound, tricuspid regurgitation pressure gradient (TRPG) and tricuspid annular plane systolic excursion (TAPSE) in the macitentan monotherapy group revealed significant differences (Z=-2.67, Z=-2.67, t=6.20, t=5.60, t=-3.04, P<0.05). There were no statistically significant differences in right ventricular diameter (RVD), right atrial diameter (RAD), ascending aortic root inner diameter (AAO) and left ventricular end-diastolic diameter (LVEDd) (P>0.05). After 24 weeks of medication, the number of patients with WHO-FC grade III/IV symptoms decreased from 6 to 3, 1 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 2, 2 to 4 respectively(P<0.05). After 24 weeks of treatment, 6MWD, NT-proBNP, LVEDd, sPAP and TRPG in the macitentan combined with sildenafil treatment group revealed statistically significant differences (Z=-4.11, Z=-3.74, Z=-3.83, t=6.88, t=6.54, P<0.001). Significant differences in RVD, RAD, and TAPSE were found (t=3.46, t=3.69, t=-3.12, P<0.05). There were no statistically significant variances in AAO between the groups (P>0.05). The number of patients with WHO-FC grade III/IV symptoms decreased from 16 to 8, 5 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 1, 2 to 14 respectively (P<0.001). There were no statistically significant differences before and after treatment in 6MWD, NT-proBNP, RVD, RAD, AAO, LVEDd, sPAP, TRPG and TAPSE between the two groups (P>0.05). There were no statistically significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr) and hemoglobin (Hb) between 0 and 24 weeks (P>0.05). Conclusions: Exercise tolerance and cardiac function in patients with CTD-PAH were significantly improved after treatment with macitentan, which was well tolerated. Therefore, macitentan may be an effective and safe targeted drug for CTD-PAH.

The impact of triglyceride glucose-body mass index on all-cause and cardiovascular mortality in elderly patients with diabetes mellitus: evidence from NHANES 2007-2016.

BACKGROUND: The relationship between triglyceride glucose-body mass index (TyG-BMI) index and mortality in elderly patients with diabetes mellitus (DM) are still unclear. This study aimed to investigate the association between TyG-BMI with all-cause and cardiovascular mortality among elderly DM patients in the United States (US). METHODS: Patients aged over 60 years with DM from the National Health and Nutrition Examination Survey (2007-2016) were included in this study. The study endpoints were all-cause and cardiovascular mortality and the morality data were extracted from the National Death Index (NDI) which records up to December 31, 2019. Multivariate Cox proportional hazards regression model was used to explore the association between TyG-BMI index with mortality. Restricted cubic spline was used to model nonlinear relationships. RESULTS: A total of 1363 elderly diabetic patients were included, and were categorized into four quartiles. The mean age was 70.0 ± 6.8 years, and 48.6% of them were female. Overall, there were 429 all-cause deaths and 123 cardiovascular deaths were recorded during a median follow-up of 77.3 months. Multivariate Cox regression analyses indicated that compared to the 1st quartile (used as the reference), the 3rd quartile demonstrated a significant association with all-cause mortality (model 2: HR = 0.64, 95% CI 0.46-0.89, P = 0.009; model 3: HR = 0.65, 95% CI 0.43-0.96, P = 0.030). Additionally, the 4th quartile was significantly associated with cardiovascular mortality (model 2: HR = 1.83, 95% CI 1.01-3.30, P = 0.047; model 3: HR = 2.45, 95% CI 1.07-5.57, P = 0.033). The restricted cubic spline revealed a U-shaped association between TyG-BMI index with all-cause mortality and a linear association with cardiovascular mortality, after adjustment for possible confounding factors. CONCLUSIONS: A U-shaped association was observed between the TyG-BMI index with all-cause mortality and a linear association was observed between the TyG-BMI index with cardiovascular mortality in elderly patients with DM in the US population.

Distinct Time-resolved Brain-wide Coactivations in Oxygenated and Deoxygenated Hemoglobin.

OBJECTIVE: Human resting-state networks (RSNs) estimated from oxygenated (HbO) and deoxygenated hemoglobin (HbR) data exhibit strong similarities, while task-based studies show different dynamics in HbR and HbO responses. Such a discrepancy might be explained due to time-averaged estimations of RSNs. Our study investigated differences between HbO and HbR on time-resolved brain-wide coactivation patterns (CAPs). APPROACH: Diffuse optical tomography was reconstructed from resting-state whole-head functional near-infrared spectroscopy data of HbR and HbO in individual healthy participants. Timeaveraged RSNs were obtained using the group-level independent component analysis. Time-resolved CAPs were estimated using a clustering approach on the time courses of all obtained RSNs. Characteristics of the RSNs and CAPs from HbR and HbO were compared. MAIN RESULTS: Spatial patterns of HbR and HbO RSNs exhibited significant similarities. Meanwhile, HbR CAPs revealed much more organized spatial and dynamic characteristics than HbO CAPs. The entire set of HbR CAPs suggests a superstructure resulted from brain-wide neuronal dynamics, which is less evident in the set of HbO CAPs. These differences between HbO and HbR CAPs were consistently replicated in individual session data. CONCLUSION: Our results suggest that human resting brain-wide neuronal activations are preserved better in time-resolved brainwide patterns, i.e., CAPs, from HbR than those from HbO, while such a difference is lost between time-averaged HbR and HbO RSNs. SIGNIFICANCE: Our results reveal, for the first time, HbR concentration fluctuations are more directly coupled with resting dynamics of brain-wide neuronal activations in human brains.

Comprehensive kinetic modeling and product distribution for pyrolysis of pulp and paper mill sludge.

Pyrolysis holds immense potential for clean treatment of pulp and paper mill sludge (PPMS), enabling efficient energy and chemical recovery. However, current understanding of PPMS pyrolysis kinetics and product characteristics remains incomplete. This study conducted detailed modeling of pyrolysis kinetics for two typical PPMSs from a wastepaper pulp and paper mill, namely, deinking sludge (PPMS-DS) and sewage sludge (PPMS-SS), and analyzed comprehensively pyrolysis products. The results show that apparent activation energy of PPMS-DS (169.25-226.82 kJ/mol) and PPMS-SS (189.29-411.21 kJ/mol) pyrolysis undergoes significant change, with numerous parallel reactions present. A distributed activation energy model with dual logistic distributions proves to be suitable for modeling thermal decomposition kinetics of both PPMS-DS and PPMS-SS, with coefficient of determination >0.999 and relative root mean square error <1.99 %. High temperature promotes decomposition of solid organic materials in PPMS, and maximum tar yield for both PPMS-DS (53.90 wt%, daf) and PPMS-SS (56.48 wt%, daf) is achieved at around 500 °C. Higher levels of styrene (24.45 % for PPMS-DS and 14.71 % for PPMS-SS) and ethylbenzene (8.61 % for PPMS-DS and 8.33 % for PPMS-SS) are detected in tar and could be used as chemicals. This work shows great potential to propel development of PPMS pyrolysis technology, enabling green and sustainable production in pulp and paper industry.

Novel manganese and nitrogen co-doped biochar based on sodium bicarbonate activation for efficient removal of bisphenol A: Mechanism insight and role analysis of manganese and nitrogen by combination of characterizations, experiments and density functional theory calculations.

A novel porous manganese and nitrogen co-doped biochar (Mn-N@SBC) was synthesized via one-step pyrolysis, utilizing loofah agricultural waste as the precursor and NaHCO3 as the activator. The behavior of bisphenol A adsorbed on Mn-N@SBC was evaluated using static batch adsorption experiments. Compared to direct manganese-nitrogen co-doping, co-doping based on NaHCO3 activation significantly increased the specific surface area (231 to 1027 m2·g-1) and adsorption capacity (15 to 351 mg·g-1). Wide pH (2-10) and good resistance to cation/anion, humic acid and actual water demonstrated the robust adaptability of Mn-N@SBC to environmental factors. The significantly reduced specific surface area after adsorption, adverse effects of ethanol and phenanthrene on the removal of bisphenol A, and theoretically predicted interaction sites indicated the primary adsorption mechanisms involved pore filling, hydrophobicity, and π-π-electron-donor-acceptor interaction. This work presented an approach to create high-efficiency adsorbents from agricultural waste, offering theoretical and practical guidance for the removal of pollutants.

Cotton swabs wrapped with three-dimensional silver nanoflowers as SERS substrates for the determination of food colorant carmine on irregular surfaces.

A lightweight, portable, low-cost, and accessible cotton swab was employed as surface enhanced Raman spectroscopy (SERS) matrix template. The silver nanoflowers were in situ grown on the surface of cotton swabs to form three-dimensional Ag nanoflower@cotton swabs (AgNF@CS) SERS substrate with high-density and multi-level hot spots. The SERS performance of AgNFs@CS substrates with various reaction time was systematically studied. The optimal AgNF-120@CS SERS substrate exhibits superior detection sensitivity of 10-10 M for methylene blue, good signal reproducibility, high enhancement factor of 1.4 × 107, and excellent storage stability (over 30 days). Moreover, the AgNF-120@CS SERS substrate also exhibits prominent detection sensitivity of 10-8 M for food colorant of carmine. Besides, the portable AgNF-120@CS SERS substrate is also capable of detecting food colorant residues on irregular food surfaces.