Visible light accelerates skin wound healing and alleviates scar formation in mice by adjusting STAT3 signaling.

During the wound healing process, the activation of signal transducer and activator of transcription 3 (STAT3) is considered crucial for the migration and proliferation of epithelial cells, as well as for establishing the inflammatory environment. However, an excessive STAT3 activation aggravates scar formation. Here we show that 450 nm blue light and 630 nm red light can differentially regulate the phosphorylation of STAT3 (p-STAT3) and its downstream cytokines in keratinocytes. Further mechanistic studies reveal that red light promotes wound healing by activating the PI3 kinase p110 beta (PI3Kß)/STAT3 signaling axis, while blue light inhibits p-STAT3 at the wound site by modulating cytochrome c-P450 (CYT-P450) activity and reactive oxygen species (ROS) generation. In a mouse scar model, skin wound healing can be significantly accelerated with red light followed by blue light to reduce scar formation. In summary, our study presents a potential strategy for regulating epithelial cell p-STAT3 through visible light to address skin scarring issues and elucidates the underlying mechanisms.

High-throughput screening for novel Bacillus thuringiensis insecticidal proteins revealed evidence that the bacterium exchanges Domain III to enhance its insecticidal activity.

Approximately 3000 Bacillus thuringiensis (Bt) isolates were screened to discover novel three-domain (3D) Cry proteins active against Helicoverpa zea (corn earworm). From 400 active isolates found during the primary screening, Cry1Ac and Cry2A, which are known to be active against H. zea, were removed using multiplex-primer PCR and high-throughput column chromatography. This process reduced the number of active cultures to 48. DNA segments encoding Domain III of these 48 cultures were amplified by PCR and sequenced. Sequencing revealed two novel Cry1B-type Domain IIIs. Further sequencing of the flanking regions of these domains revealed that one was part of Cry1Bj (GenBank: KT952325). However, the other Domain III lacked Domains I and II. Instead, this Domain III was associated with two open reading frames, ORF1 and ORF2. ORF1 was identified as an ATP-binding protein, and ORF2 as an ATPase, suggesting that Bt exchanges Domain III among homologous Cry proteins.

The combination of hydrogels and rutin-loaded black phosphorus nanosheets treats rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation, joint pain, and cartilage degradation. The fluctuating nature of RA often necessitates long-term oral administration of treatment drugs, which can unfortunately lead to adverse effects such as gastrointestinal discomfort and hepatic and renal dysfunction. Therefore, a percutaneous local delivery method for the release of inflammatory modulators in arthritic joints represents a promising therapeutic approach for RA. In this study, we have developed a unique and innovative therapeutic platform (named BP-Rut@Gel). This hydrogel was formulated by incorporating the drug Rutin (Rut) into Black phosphorus nanosheets (BP) and subsequently integrating them within a Hyaluronic Acid (HA) and Polyvinyl Alcohol (PVA) matrix to create a composite hydrogel. Notably, Secondly, photothermal therapy (PTT) under Near-Infrared Irradiation (NIR) and anti-inflammatory drugs synergistically worked together to efficiently quell inflammation and enhance therapeutic effectiveness. Additionally, toxicity experiments have revealed that our synthesized black phosphorus nanosheet composite hydrogel possesses excellent biocompatibility and significantly reduces the inflammatory response in RA joints. Given these remarkable properties, our BP-Rut@Gel hydrogel held significant promise and demonstrated immense clinical potential for the treatment of RA.

Kilowatt-level supercontinuum generation employing a homemade taper-shaped ytterbium-doped fiber amplifier.

A simple generation method of high-power supercontinuum (SC) based on a homemade long ytterbium-doped taper fiber (T-YDF) amplifier has been demonstrated experimentally and analyzed in this work. The power and spectra of the obtained SC are made adjustable by changing the seed pulse repetition rates. Under a 7.5 MHz seed pulse repetition rate, a SC output is obtained with a spectral range of 1000 nm-1650 nm, maximum output power of 1066 W, and conversion efficiency of 75.7%. The core/clad diameters of the homemade T-YDF are ∼20/400 µm and ∼30/600 µm at the input and output ends, respectively, and the total length is 25 m. Such a long taper fiber can further enhance the properties of the SC while ensuring high power and good beam quality. To the best of the authors' knowledge, this is the first report of directly generating a high average power SC based on the T-YDF amplifier, which provides a proof-of-concept experiment to achieve a high average power SC source and greatly improves the potential application value of the SC source.

Salinirarus marinus gen. nov., sp. nov., Haloplanus salilacus sp. nov., Haloplanus pelagicus sp. nov., Haloplanus halophilus sp. nov., Haloplanus halobius sp. nov., halophilic archaea isolated from commercial coarse salts with potential as starter cultures for salt-fermented foods.

Five halophilic archaeal strains, XH8T, CK5-1T, GDY1T, HW8-1T, and XH21T, were isolated from commercial coarse salt produced in different regions of China. Their 16S rRNA and rpoB' gene sequences indicated that four of the strains (CK5-1T, GDY1T, HW8-1T, and XH21T) represent distinct species within the genus Haloplanus (family Haloferacaceae), while strain XH8T represents a novel genus within the same family. These assignments were supported by phylogenetic and phylogenomic analyses, which showed that strains CK5-1T, GDY1T, HW8-1T, and XH21T cluster with the current species of the genus Haloplanus, while strain XH8T forms a separate branch from the genus Haloplanus. The digital DNA-DNA hybridization and average amino acid identity (AAI) values among these four strains and the current members of the genus Haloplanus were 23.1-35.2% and 75.9-83.8%, respectively; and those values between strain XH8T and other genera in the family Haloferacaceae were 18.8-33.6% and 59.8-66.6%, respectively, much lower than the threshold values for species demarcation. Strain XH8T may represent a novel genus of the family Haloferacaceae according to the cut-off value of AAI (≤72.1%) proposed to differentiate genera within the family Haloferacaceae. These five strains could be distinguished from the related species according to differential phenotypic characteristics. Based on these results, it is proposed that strain XH8T represents a novel genus within the family Haloferacaceae, and strains CK5-1T, GDY1T, HW8-1T, and XH21T represent four novel species of the genus Haloplanus, respectively. Additionally, these five strains possess genes encoding enzymes critical for the fermentation process in salt-fermented foods, indicating their potential as starter cultures for these applications.

Recoverability of zebrafish from decabromodiphenyl ether exposure: The persisted interference with extracellular matrix production and collagen synthesis and the enhancement of arrhythmias.

As a widely used brominated flame retardant, the widespread presence of decabromodiphenyl ether (BDE-209) in the natural environment and the toxicity risks it poses are well established, but the recoverability of BDE-209-induced individual injuries remains unknown. Therefore, a 7-day depuration experiment following a 4-day exposure of zebrafish to BDE-209 was conducted to confirm the recoverability and its mode of action. Oxidative stress after depuration was significantly reduced compared with BDE-209 exposure as indicated by the decreased expression level of oxidative stress-related genes and the reduced MDA, Gpx, and GST in zebrafish, indicating a gradual recovery of antioxidant activity. However, BDE-209 inhibition of extracellular matrix (ECM) proteins worsened after depuration. Mechanistically, BDE-209 mediated ECM production and secretion by down-regulating integrin expression. Furthermore, BDE-209 inhibition of collagen synthesis worsened after depuration. Biochemical assays and histopathological observations revealed a same result in zebrafish. Mechanistically, lysine hydroxylation is inhibited thereby affecting collagen synthesis. Interestingly, zebrafish showed arrhythmia after depuration compared to BDE-209 exposure, and abnormal changes in ATPase levels indicated that disturbances in Ca2+ homeostasis contributed to arrhythmia. Collectively, BDE-209-induced interference with ECM production and collagen synthesis persisted after depuration, which will provide new insights for understanding the recovery patterns of individuals under BDE-209 stress.

Chlorogenic Acid Enhances the Intestinal Health of Weaned Piglets by Inhibiting the TLR4/NF-κB Pathway and Activating the Nrf2 Pathway.

Chlorogenic acid (CGA) is a natural polyphenol with potent antioxidant and anti-inflammatory activities. However, the exact role of it in regulating intestinal health under oxidative stress is not fully understood. This study aims to investigate the effects of dietary CGA supplementation on the intestinal health of weaned piglets under oxidative stress, and to explore its regulatory mechanism. Twenty-four piglets were randomly divided into two groups and fed either a basal diet (CON) or a basal diet supplemented with 200 mg/kg CGA (CGA). CGA reduced the diarrhea rate, increased the villus height in the jejunum, and decreased the crypt depth in the duodenum, jejunum, and ileum of the weaned piglets (p < 0.05). Moreover, CGA increased the protein abundance of Claudin-1, Occludin, and zonula occludens (ZO)-1 in the jejunum and ileum (p < 0.05). In addition, CGA increased the mRNA expression of pBD2 in the jejunum, and pBD1 and pBD2 in the ileum (p < 0.05). The results of 16S rRNA sequencing showed that CGA altered the ileal microbiota composition and increased the relative abundance of Lactobacillus reuteri and Lactobacillus pontis (p < 0.05). Consistently, the findings suggested that the enhancement of the intestinal barrier in piglets was associated with increased concentrations of T-AOC, IL-22, and sIgA in the serum and T-AOC, T-SOD, and sIgA in the jejunum, as well as T-AOC and CAT in the ileum caused by CGA (p < 0.05). Meanwhile, CGA decreased the concentrations of MDA, IL-1ß, IL-6, and TNF-α in the serum and jejunum and IL-1ß and IL-6 in the ileum (p < 0.05). Importantly, this study found that CGA alleviated intestinal inflammation and oxidative stress in the piglets by inhibiting the TLR4/NF-κB signaling pathway and activating the Nrf2 signaling pathway. These findings showed that CGA enhances the intestinal health of weaned piglets by inhibiting the TLR4/NF-κB pathway and activating the Nrf2 pathway.

Visible-Light-Promoted Reduction of Nitroarenes with Formate Salts as Reductants.

A visible-light-promoted reduction of nitrobenzenes using formate salts as the reductant was developed. A wide range of nitrobenzenes can be converted into aniline products in a transition metal free fashion. Mechanistic studies revealed that radical species (carbon dioxide radical anion and thiol radical) are key intermediates for the transformation. We anticipate that this method will provide a valuable and green strategy for the reduction of nitrobenzenes.

Synthesis of ß-Silyl Amines via Merging Photoinduced Energy and Hydrogen Atom Transfer in Flow.

The development of efficient methods for synthesizing ß-silyl amines has long been a significant goal in organic synthesis. Previous methods mainly relied on the use of prefunctionalized substrates or special reagents. Herein, we present a visible-light-promoted synthesis approach for ß-silyl amines, utilizing a combination of photoinduced energy and hydrogen atom transfer processes. Using flow chemistry technology, a variety of valuable skeletons, including ß-silyl amines and α-amino esters, can be produced from readily available feedstocks such as hydrosilanes and simple alkanes. Moreover, the strategy's full-process fluidized production capability highlights its potential for industrial-scale manufacturing. Mechanistic studies revealed that oxime esters can act as radical precursors as well as hydrogen atom transfer reagents.

Integrative radiopathomics model for predicting progression-free survival in patients with nonmetastatic nasopharyngeal carcinoma.

PURPOSE: To construct an integrative radiopathomics model for predicting progression-free survival (PFS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients. METHODS: 357 NPC patients who underwent pretreatment MRI and pathological whole-slide imaging (WSI) were included in this study and randomly divided into two groups: a training set (n = 250) and validation set (n = 107). Radiomic features extracted from MRI were selected using the minimum redundancy maximum relevance and least absolute shrinkage and selection operator methods. The pathomics signature based on WSI was constructed using a deep learning architecture, the Swin Transformer. The radiopathomics model was constructed by incorporating three feature sets: the radiomics signature, pathomics signature, and independent clinical factors. The prognostic efficacy of the model was assessed using the concordance index (C-index). Kaplan-Meier curves for the stratified risk groups were tested by the log-rank test. RESULTS: The radiopathomics model exhibited superior predictive performance with C-indexes of 0.791 (95% confidence interval [CI]: 0.724-0.871) in the training set and 0.785 (95% CI: 0.716-0.875) in the validation set compared to any single-modality model (radiomics: 0.619, 95% CI: 0.553-0.706; pathomics: 0.732, 95% CI: 0.662-0.802; clinical model: 0.655, 95% CI: 0.581-0.728) (all, P < 0.05). The radiopathomics model effectively stratified patients into high- and low-risk groups in both the training and validation sets (P < 0.001). CONCLUSION: The developed radiopathomics model demonstrated its reliability in predicting PFS for NPC patients. It effectively stratified individual patients into distinct risk groups, providing valuable insights for prognostic assessment.

Aged bone marrow macrophages drive systemic aging and age-related dysfunction via extracellular vesicle-mediated induction of paracrine senescence.

The accumulation and systemic propagation of senescent cells contributes to physiological aging and age-related pathology. However, which cell types are most susceptible to the aged milieu and could be responsible for the propagation of senescence has remained unclear. Here we found that physiologically aged bone marrow monocytes/macrophages (BMMs) propagate senescence to multiple tissues, through extracellular vesicles (EVs), and drive age-associated dysfunction in mice. We identified peroxisome proliferator-activated receptor α (PPARα) as a target of microRNAs within aged BMM-EVs that regulates downstream effects on senescence and age-related dysfunction. Demonstrating therapeutic potential, we report that treatment with the PPARα agonist fenofibrate effectively restores tissue homeostasis in aged mice. Suggesting conservation to humans, in a cohort study of 7,986 participants, we found that fenofibrate use is associated with a reduced risk of age-related chronic disease and higher life expectancy. Together, our findings establish that BMMs can propagate senescence to distant tissues and cause age-related dysfunction, and they provide supportive evidence for fenofibrate to extend healthy lifespan.

Disruption of glucose homeostasis by bacterial infection orchestrates host innate immunity through NAD+/NADH balance.

Metabolic reprogramming is crucial for activating innate immunity in macrophages, and the accumulation of immunometabolites is essential for effective defense against infection. The NAD+/NADH (ratio of nicotinamide adenine dinucleotide and its reduced counterpart) redox couple serves as a critical node that integrates metabolic pathways and signaling events, but how this metabolite couple engages macrophage activation remains unclear. Here, we show that the NAD+/NADH ratio serves as a molecular signal that regulates proinflammatory responses and type I interferon (IFN) responses divergently. Salmonella Typhimurium infection leads to a decreased NAD+/NADH ratio by inducing the accumulation of NADH. Further investigation shows that an increased NAD+/NADH ratio correlates with attenuated proinflammatory responses and enhanced type I IFN responses. Conversely, a decreased NAD+/NADH ratio is linked to intensified proinflammatory responses and restrained type I IFN responses. These results show that the NAD+/NADH ratio is an essential cell-intrinsic factor that orchestrates innate immunity, which enhances our understanding of how metabolites fine-tune innate immunity.

Genome-Wide Identification and Characterization of Maize Long-Chain Acyl-CoA Synthetases and Their Expression Profiles in Different Tissues and in Response to Multiple Abiotic Stresses.

Long-chain acyl-CoA synthetases (LACSs) are essential enzymes that activate free fatty acids to fatty acyl-CoA thioesters, playing key roles in fatty acid (FA) catabolism, lipid synthesis and storage, epidermal wax synthesis, and stress tolerance. Despite their importance, comprehensive information about LACS genes in maize, a primary food crop, remains scarce. In the present work, eleven maize LACS genes were identified and mapped across five chromosomes. Three pairs of segmentally duplicated genes were detected in the maize LACS gene family, which underwent significant purifying selection (Ka/Ks < 1). Subsequently, phylogenetic analysis indicated that ZmLACS genes were divided into four subclasses, as supported by highly conserved motifs and gene structures. On the basis of the PlantCARE database, analysis of the ZmLACS promoter regions revealed various cis-regulatory elements related to tissue-specific expression, hormonal regulation, and abiotic stress response. RT-qPCR analysis showed that ZmLACS genes exhibit tissue-specific expression patterns and respond to diverse abiotic stresses including drought and salt, as well as phytohormone abscisic acid. Furthermore, using the STRING database, several proteins involved in fatty acid and complex lipid synthesis were identified to be the potential interaction partners of ZmLACS proteins, which was also confirmed by the yeast two-hybrid (Y2H) assay, enhancing our understanding of wax biosynthesis and regulatory mechanisms in response to abiotic stresses in maize. These findings provide a comprehensive understanding of ZmLACS genes and offer a theoretical foundation for future research on the biological functions of LACS genes in maize environmental adaptability.

A recoverable hydrophilic deep eutectic solvent for efficient extraction of polyphenolic compounds from raspberry root.

Green deep eutectic solvents (DESs) are widely used to extract bioactive components from plant biomass; however, hydrophilic DES and bioactive component isolation methods have not been developed. In this study, we synthesized hydrophilic DES (CL-CA-DES) using citric acid and choline chloride. We combined this with environmentally friendly anion- and cation-exchange resin column chromatographic isolation methods. This approach extracted and isolated four polyphenolic compounds (catechins, epicatechins, procyanidin B1, and procyanidin B2) from raspberry root and efficiently recovered the hydrophilic DES. CL-CA-DES extracted significantly higher contents of catechin and procyanidin B2 from raspberry root compared to other solvents. It also extracted substantially higher contents of epicatechin compared to butyl alcohol, 70% ethanol, and water, but there was no significant difference when compared with acetone and ethyl acetate. Additionally, CL-CA-DES extracted significantly higher contents of procyanidin B1 compared to butyl alcohol, water, and ethyl acetate, with no significant difference when compared with 70% ethanol and acetone. The isolation efficiency of the bioactive components in the raspberry root extract by anion- and cation-exchange resin column chromatography was higher than that of the organic solvent extraction and precipitation generation methods, and the method was effective in recovering CL-CA-DES with a recovery rate higher than 60%. In conclusion, this study developed a new method for the efficient recovery of hydrophilic CL-CA-DES, which can be used for isolating polyphenolic compounds from raspberry root.

A phase II study of post-remission therapy with pembrolizumab in older patients with acute myeloid leukemia.

Not available.

The role and mechanism of AMPK in pulmonary hypertension.

Pulmonary hypertension (PH) is a chronic progressive disease with high mortality. There has been more and more research focusing on the role of AMPK in PH. AMPK consists of three subunits-α, ß, and γ. The crosstalk among these subunits ultimately leads to a delicate balance to affect PH, which results in conflicting conclusions about the role of AMPK in PH. It is still unclear how these subunits interfere with each other and achieve balance to improve or deteriorate PH. Several signaling pathways are related to AMPK in the treatment of PH, including AMPK/eNOS/NO pathway, Nox4/mTORC2/AMPK pathway, AMPK/BMP/Smad pathway, and SIRT3-AMPK pathway. Among these pathways, the role and mechanism of AMPK/eNOS/NO and Nox4/mTORC2/AMPK pathways are clearer than others, while the SIRT3-AMPK pathway remains still unclear in the treatment of PH. There are drugs targeting AMPK to improve PH, such as metformin (MET), MET combination, and rhodiola extract. In addition, several novel factors target AMPK for improving PH, such as ADAMTS8, TUFM, and Salt-inducible kinases. However, more researches are needed to explore the specific AMPK signaling pathways involved in these novel factors in the future. In conclusion, AMPK plays an important role in PH.

The High Resistance Loop (H-Loop) Technique for Arthroscopic Repair of Subscapularis.

The subscapularis tendon is more challenging and riskier to repair than the posterior upper rotator cuff. The knotless anchor suture in subscapularis repair simplified the repair process and had an excellent postoperative effect. We describe a new knotless anchor stitching method, the H-Loop technique. The simplicity and efficiency of the technique make it particularly suitable for small subscapular tendon tears.

Imaging-based surrogate classification for risk stratification of hepatocellular carcinoma with microvascular invasion to adjuvant hepatic arterial infusion chemotherapy: a multicenter retrospective study.

BACKGROUND: Patients with microvascular invasion (MVI)-positive hepatocellular carcinoma (HCC) have shown promising results with adjuvant hepatic arterial infusion chemotherapy (HAIC) with FOLFOX after curative resection. We aim to develop an imaging-derived biomarker to depict MVI-positive HCC patients more precisely and promote individualized treatment strategies of adjuvant HAIC. MATERIALS AND METHODS: Patients with MVI-positive HCC were identified from five academic centers and utilized for model development (n=470). Validation cohorts were pooled from a previously reported prospective clinical study conducted (control cohort (n=145), adjuvant HAIC cohort (n=143)) (NCT03192618). The primary endpoint was recurrence-free survival (RFS). Imaging features were thoroughly reviewed, and multivariable logistic regression analysis was employed for model development. Transcriptomic sequencing was conducted to identify the associated biological processes. RESULTS: Arterial phase peritumoral enhancement, boundary of the tumor enhancement, tumor necrosis stratification, and boundary of the necrotic area were selected and incorporated into the nomogram for RFS. The imaging-based model successfully stratified patients into two distinct prognostic subgroups in both the training, control, and adjuvant HAIC cohorts (median RFS, 6.00 vs. 66.00 mo, 4.86 vs. 24.30 mo, 11.46 vs. 39.40 mo, all P<0.01). Furthermore, no significant statistical difference was observed between patients at high-risk of adjuvant HAIC and those in the control group (P=0.61). The area under the receiver operating characteristic curve at two years was found to be 0.83, 0.84, and 0.73 for the training, control, and adjuvant HAIC cohorts respectively. Transcriptomic sequencing analyses revealed associations between the radiological features and immune-regulating signal transduction pathways. CONCLUSION: The utilization of this imaging-based model could help to better characterize MVI-positive HCC patients and facilitate the precise subtyping of patients who genuinely benefit from adjuvant HAIC treatment.

Macrophage-derived extracellular vesicles regulate skeletal stem/progenitor Cell lineage fate and bone deterioration in obesity.

Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.