Signalling by senescent melanocytes hyperactivates hair growth.

Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi in human often display excessive hair growth, suggesting hair stem cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters of senescent melanocytes drive epithelial hair stem cells to exit quiescence and change their transcriptome and composition, potently enhancing hair renewal. Nevus melanocytes activate a distinct secretome, enriched for signalling factors. Osteopontin, the leading nevus signalling factor, is both necessary and sufficient to induce hair growth. Injection of osteopontin or its genetic overexpression is sufficient to induce robust hair growth in mice, whereas germline and conditional deletions of either osteopontin or CD44, its cognate receptor on epithelial hair cells, rescue enhanced hair growth induced by dermal nevus melanocytes. Osteopontin is overexpressed in human hairy nevi, and it stimulates new growth of human hair follicles. Although broad accumulation of senescent cells, such as upon ageing or genotoxic stress, is detrimental for the regenerative capacity of tissue4, we show that signalling by senescent cell clusters can potently enhance the activity of adjacent intact stem cells and stimulate tissue renewal. This finding identifies senescent cells and their secretome as an attractive therapeutic target in regenerative disorders.

Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of acute lung inflammation in male mice.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein-pseudotyped (Spp) lentivirus with the proper tropism of the SARS-CoV-2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild-type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV-G) or with a deletion of the receptor-binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27-75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3-5 times more viral burden from Spp lentivirus than from VSV-G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR-γ were quickly upregulated in response to infection in the lungs as well as in macrophage-like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS-CoV-2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2-independent viral entry pathway may be recruited in the heart and aorta.

Changes in intestinal microbiota and correlation with TLRs in ulcerative colitis in the coastal area of northern China.

OBJECTIVE: To investigate the communities of fecal microbiota and the role of Toll-like receptors in patients with ulcerative colitis in the coastal area of northern China. METHODS: Stool samples from 31 patients with ulcerative colitis and 12 healthy individuals were collected. The total bacterial genomic DNA was extracted, and the V3+V4 hypervariable region in the bacterial 16S rRNA gene sequence was amplified by polymerase chain reaction (PCR). High-throughput sequencing analysis was performed on the Illumina Hiseq platform. The expression of TLR2, TLR4, Tollip, PPAR-γ, IL-6, and TNF-α in the colonic mucosa was measured by Western blots. RESULTS: The diversity of the fecal microbiota in patients with ulcerative colitis was significantly less than that in healthy control individuals (p < 0.05). The proportion of Bacteroidetes was significantly reduced (p < 0.01), whereas Proteobacteria was prevalent (p < 0.01) in patients with ulcerative colitis. At the genus level, the relative abundance of Streptococcus and Anaerostipes was significantly increased (p < 0.05), whereas the proportion of Bacteroides, Lachnospira, Ruminococcus, Phascolarctobacterium, and Coprococcus was significantly decreased in patients with ulcerative colitis (p < 0.05). The diversity indexes of fecal microbiota in patients with ulcerative colitis were negatively correlated with disease severity (p < 0.05). The relative abundance of Enterobacteriaceae was positively correlated with disease severity, and the relative abundance of Phascolarctobacterium, Anaerostipes, Fusobacterium, Parabacteroides, Oscillospira, and Ochrobactrum were negatively correlated with disease severity. The expression levels of TLR2 and TLR4 in the intestinal mucosa were positively correlated with the relative abundance of Streptococcus and Enterobacteriaceae, respectively (r = 0.481, p = 0.007; r = 0.455, p = 0.017). CONCLUSION: There were significant changes in the diversity and composition of the fecal microbiota in patients with ulcerative colitis compared to healthy individuals. The dysbiosis of gut microbiota and correlation with TLRs might play important roles in the pathogenesis and progression of ulcerative colitis.

Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients.

BACKGROUND: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. OBJECTIVE: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. METHODS: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. RESULTS: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients. CONCLUSIONS: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.

Fecal occult blood and urinary cytology tests for rapid screening of inflammatory infection in the gastrointestinal and urological systems in patients with Coronavirus disease 2019.

BACKGROUND: Gastrointestinal infections (GI) and urological infections (UI) have not been fully addressed in COVID-19 patients. We aimed to evaluate the values of routine fecal occult blood (FOB) test and urinary cytology test (UCT) for screening of GI and UI in COVID-19 patients. METHODS: In this retrospective study, COVID-19 patients without associated comorbidities were divided into FOB- or UCT-positive or FOB- or UCT-negative groups. Their clinical characteristics and laboratory findings were then compared. RESULTS: A total of 13.6% of patients (47 of 345) tested positive for FOB, and 57.4% (27 of 47) of these patients lacked gastrointestinal symptoms. A total of 30.1% of patients (104 of 345) exhibited gastrointestinal symptoms, and 38.0% (131 of 345) were positive for either FOB or gastrointestinal symptoms. FOB-positive patients possessed significantly higher levels of C-reactive protein and fewer lymphocytes than FOB-negative patients. A total of 36.9% of patients (80 of 217) exhibited positive UCT, and 97.5% (78 of 80) of these patients possessed normal levels of serum markers for renal injuries. Significant differences in age and sex ratios were observed between the UCT-positive and UCT-negative groups, and 72.4% (42 of 58) of female patients over 60 years old were UCT-positive. CONCLUSIONS: Fecal occult blood test in combination with gastrointestinal symptoms could serve as a simple and useful screening approach for GI diagnoses for COVID-19. Age and sex are risk factors for UI in COVID-19 patients. UCT could be a sensitive tool for assessing early UI at a stage in which serum markers for renal injuries appear normal.

Biomarker Prediction of Postoperative Healing of Diabetic Foot Ulcers: A Retrospective Observational Study of Serum Albumin.

PURPOSE: The purpose of this study was to investigate the relationship and to determine potential usefulness of serum albumin as a biomarker for predicting postoperative diabetic foot ulcer (DFU) healing. DESIGN: A retrospective study. SUBJECTS AND SETTING: The sample comprised 266 inpatients with type 2 diabetes receiving care in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Among them, 174 had DFUs and underwent surgery for foot DFUs including amputation, skin grafting, and flap procedures. A comparison group consisted of 92 inpatients without a DFU or surgery. METHODS: The association between healing and preoperative albumin levels was analyzed via a logistic regression model and receiver operating characteristic (ROC) curve. RESULTS: The albumin value of patients with DFU grade 3 or more (3.23 ± 0.58 g/dL) was lower than that of patients with DFU grade 1-2 (3.58 ± 0.5 g/dL), and both were lower than that of the comparison group (3.89 ± 0.3 g/dL). Patients with a DFU with hypoalbuminemia (<3.5 g/dL) had a 2.5-fold higher risk of nonhealing at postoperative 28 days than patients with normal levels (odds ratio = 3.51; 95% confidence interval, 1.75-7.06; P < .001). For patients with a DFU overall, the ROC curve showed a preoperative albumin cutoff of 3.44 g/dL for DFU wound healing. CONCLUSIONS: For patients with a DFU undergoing surgery, preoperative serum albumin may be used as a biomarker for predicting postoperative healing.

Cholesterol: A new game player accelerating vasculopathy caused by SARS-CoV-2?

The pandemic of coronavirus disease (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19, including lungs, heart, kidney, liver, brain, and vascular system. Patients with metabolic-associated preconditions, such as hypertension, obesity, and diabetes, are susceptible to experiencing severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in patients with COVID-19. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.

Elevations of serum cancer biomarkers correlate with severity of COVID-19.

In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 µg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 µg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 µg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 µg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.

Trivalent iron-tartaric acid metal-organic framework for catalytic ozonation of succinonitrile.

As porous crystal materials, metal-organic frameworks (MOFs) have attracted wide attention in the field of environmental remediation. In this study, a trivalent iron-tartaric acid metal-organic framework (T2-MOF) was successfully synthesized using the inexpensive raw materials ferric chloride (FeCl3.6H2O) and tartaric acid (C4H6O6). The physical and chemical properties of T2-MOF were studied by using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller. After that, T2-MOF was used as a catalyst for catalytic ozonation of succinonitrile. The results show that T2-MOF has obvious crystal characteristics and uniform structure. In addition, T2-MOF exhibits strong catalytic performance in ozonation of succinonitrile. The results indicate that the chemical oxygen demand (COD) removal rate is affected by various operating parameters including catalyst characteristics dosages and initial pH values. In the ozonation with 30 mg L-1 T2-MOF, the COD removal rate of 100 mg L-1 succinonitrile reached 73.1% (±4.6%) within 180 min, which was 67.3% (±4.4%) higher than that obtained in the process without catalyst. T2-MOF maintained strong catalytic performance with the pH range of 3.0-7.0. By monitoring the Fe2+ concentration at different reaction time, it was found that the homogeneous catalysis occurred simultaneously with the heterogeneous catalysis.

Mineralization of petrochemical wastewater after biological treatment by ozonation catalyzed with divalent iron tartaric acid chelate.

The petrochemical wastewater includes many toxic organic compounds, which are refractory substances. It is difficult for the wastewater to meet discharge standards after biological treatment, therefore, the further effective treatment of post-biochemical petrochemical wastewater has become an urgent problem to be solved. This study used iron tartaric acid chelate (ITC) catalytic ozonation to treat the petrochemical wastewater. Various key factors were investigated, such as hydraulic retention time (HRT), catalyst dosage, ozone concentration, initial pH values and oxidation efficiency. The kinetics of catalytic ozonation were established. The results indicate that the chemical oxygen demand (COD) removal rate reached a maximum of 58.5%, when the Fe2+ dosage is 0.25 mmol L-1, the initial pH value is neutral, the liquid phase ozone concentration is about 1.95 mg L-1, and HRT is equal to 180 min. In addition, when HRT is equal to 90 min, the B/C ratio of wastewater increases to 0.31, the catalytic ozone reaches maximum oxidation efficiency, and the most economical HRT was 90 min. Finally, the kinetics of ITC catalytic ozonation catalyzed with ITC is consistent with the pseudo-first-order kinetic reaction, and its rate constant is 0.00484 min-1.

Characteristics of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)-Induced Small Bowel Injury Identified by Single-Balloon Endoscopy or Capsule Endoscopy.

BACKGROUND The special features of nonsteroidal anti-inflammatory drugs (NSAIDs) enteropathy were partially clarified by single-balloon endoscopy(SBE). We aimed to investigate the characteristics of NSAIDs injuries that were differ from other ulcer diseases and efficacy of SBE compared with capsule endoscopy(CE). MATERIAL AND METHODS 1,644 symptomatic patients (221 patients taking NSAIDs) hospitalized between January 2006 and March 2016 were recruited and underwent SBE and/or CE. RESULTS NSAIDs damages were identified in 110 patients (49.77%). The special features of NSAIDs lesions included: variform, superficial, multiple and irregular arrangement; <1 cm in diameter (67.27%); the location in jejunum and ileum was similar; ileocecal valve was rarely influenced (20.91%). The specificity and positive predictive value of SBE for diagnosing NSAIDs breaks were higher than CE (95.74% vs. 80.00%; 95.45% vs. 81.63%, p<0.05). There were no differences in the detection rate and the diagnostic accuracy rate of small bowel diseases between SBE and CE in the NSAIDs group (69.4% vs. 66.3% and 83.58% vs. 80.65%, p>0.05 respectively). The consistency in diagnosing NSAIDs breaks for the 2 methods was 82.61%. More tiny lesions at the distal ileum were detected by SBE. Four patients misdiagnosed by CE got accurate diagnose through biopsy by SBE. Three patients with active bleeding caused by NSAIDs-induced ulcers underwent hemostasis successfully by SBE. CONCLUSIONS NSAIDs injuries might be distinguished from other diseases by endoscopic features and biopsy through SBE, which appeared to be an effective method for diagnosis and treatment.

Co-Delivery of Astaxanthin and siTGF-ß1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy.

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor ß1 (siTGF-ß1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-ß1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-ß1, delivered by ASNPs, significantly silenced the expression of TGF-ß1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-ß1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

Ultra-sensitive and rapid detection of Salmonella enterica and Staphylococcus aureus to single-cell level by aptamer-functionalized carbon nanotube field-effect transistor biosensors.

Foodborne diseases caused by Salmonella enterica (S. enterica) and Staphylococcus aureus (S. aureus) significantly impact public health, underscoring the imperative for highly sensitive, rapid, and accurate detection technologies to ensure food safety and prevent human diseases. Nanomaterials hold great promise in the development of high-sensitivity transistor biosensors. In this work, field-effect transistor (FET) comprising high-purity carbon nanotubes (CNTs) were fabricated and modified with corresponding nucleic acid aptamers for the high-affinity and selective capture of S. enterica and S. aureus. The aptamer-functionalized CNT-FET biosensor demonstrated ultra-sensitive and rapid detection of these foodborne pathogens. Experimental results indicated that the biosensor could detect S. enterica at a limit of detection (LOD) as low as 1 CFU in PBS buffer, and S. aureus at an LOD of 1.2 CFUs, achieving single-cell level detection accuracy with exceptional specificity. The biosensor exhibited a rapid response time, completing single detections within 200 s. Even in the presence of interference from six complex food matrices, the biosensor maintained its ultra-sensitive (3.1 CFUs) and rapid response (within 200 s) characteristics for both pathogens. The developed aptamer-functionalized CNT-FET biosensor demonstrates a capability for low-cost, ultra-sensitive, label-free, and rapid detection of low-abundance S. enterica and S. aureus in both buffer solutions and complex environments. This innovation holds significant potential for applying this detection technology to on-site rapid testing scenarios, offering a promising solution to the pressing need for efficient and reliable pathogen monitoring in various settings.

Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study.

Objective: Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis. Methods: We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results. Results: According to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis. Objective conclusion: There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.

The naringin/carboxymethyl chitosan/sodium hyaluronate/silk fibroin scaffold facilitates the healing of diabetic wounds by restoring the ROS-related dysfunction of vascularization and macrophage polarization.

Chronic diabetic wounds remain a globally recognized clinical challenge, which occurs mainly due to the disturbances of wound microenvironmental induced by high concentrations of reactive oxygen species (ROS). Impairments in angiogenesis and inflammation in the wound microenvironment ultimately impede the normal healing process. Therefore, targeting macrophage and vascular endothelial cell dysfunction is a promising therapeutic strategy. In our study, we fabricated artificial composite scaffolds composed of naringin/carboxymethyl chitosan/sodium hyaluronate/silk fibroin (NG/CMCS/HA/SF) to promote wound healing. The NG/CMCS/HA/SF scaffold demonstrated favorable anti-inflammatory, anti-oxidative, and pro-angiogenic properties in both in vitro and in vivo experiments, effectively promoting the healing of diabetic wounds. The positive therapeutic effects observed indicate that the composite scaffolds have great potential in clinical wound healing applications.

Abnormal brain glucose metabolism patterns in patients with advanced non-small-cell lung cancer after chemotherapy：A retrospective PET study.

PURPOSE: This study was designed to investigate the acute or chronic post-chemotherapy effect and different chemotherapy cycles effect on brain glucose metabolism. METHODS: A total of seventy-three patients who received chemotherapy after being diagnosed with advanced non-small-cell lung cancer (NSCLC) and underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan at Nuclear Medicine Department of the Fifth Hospital of Sun Yat-sen University between September 2017 and August 2022 were included. Seventy-two healthy control patients who underwent whole-body 18F-FDG PET/CT scans at our department, without any evidence of malignancy and confirmed by follow-up visits, were included. Advanced NSCLC patients were classified into six arms: short-to-long course (chemotherapy cycles under 4, between 5 and 8 and more than 8) in acute chemotherapy effect (AC) group (scanned 18F-FDG PET/CT within 6 months post-chemotherapy) or chronic chemotherapy effect (CC) group (the interval between scanning and the last chemotherapy session more than six months). Statistical Parametric Mapping (SPM) analysis between patients' groups and healthy controls' brain 18F-FDG PET was performed (uncorrected p ˂ 0.001 with cluster size above 20 contiguous voxels). RESULTS: There were no significant differences between patients' groups and healthy controls in age, gender and body mass index (BMI). SPM PET analyses revealed anomalous brain metabolic activity in different groups (p ˂ 0.001). Short-course + AC group exhibited hypermetabolism in the cerebellum and widespread hypometabolism in bilateral frontal lobe predominantly. Only hypometabolic brain regions were observed in middle-course + AC patients. Long-course + AC group displayed a greater number of abnormalities. Notably, these metabolic abnormalities tended to decrease in CC groups versus AC groups across all courses. CONCLUSION: Our study revealed that patients with advanced NSCLC who underwent chemotherapy exhibited persistent abnormal brain metabolism patterns during continuous chemotherapy and these abnormalities tended to recover after completion of chemotherapy over time, but without correlation to an increasing number of chemotherapy cycles. 18F-FDG PET/CT may serve as a possible modality for evaluating brain function and guiding appropriate treatment timing.

Fibroblast growth factor 8 facilitates cell-cell communication in chondrocytes via p38-MAPK signaling.

Gap junction intercellular communication (GJIC) is essential for regulating the development of the organism and sustaining the internal environmental homeostasis of multi-cellular tissue. Fibroblast growth factor 8 (FGF8), an indispensable regulator of the skeletal system, is implicated in regulating chondrocyte growth, differentiation, and disease occurrence. However, the influence of FGF8 on GJIC in chondrocytes is not yet known. The study aims to investigate the role of FGF8 on cell-cell communication in chondrocytes and its underlying biomechanism. We found that FGF8 facilitated cell-cell communication in living chondrocytes by the up-regulation of connexin43 (Cx43), the major fundamental component unit of gap junction channels in chondrocytes. FGF8 activated p38-MAPK signaling to increase the expression of Cx43 and promote the cell-cell communication. Inhibition of p38-MAPK signaling impaired the increase of Cx43 expression and cell-cell communication induced by FGF8, indicating the importance of p38-MAPK signaling. These results help to understand the role of FGF8 on cell communication and provide a potential cue for the treatment of cartilage diseases.

Ultraflexible, cost-effective and scalable polymer-based phase change composites via chemical cross-linking for wearable thermal management.

Phase change materials (PCMs) offer great potential for realizing zero-energy thermal management due to superior thermal storage and stable phase-change temperatures. However, liquid leakage and solid rigidity of PCMs are long-standing challenges for PCM-based wearable thermal regulation. Here, we report a facile and cost-effective chemical cross-linking strategy to develop ultraflexible polymer-based phase change composites with a dual 3D crosslinked network of olefin block copolymers (OBC) and styrene-ethylene-butylene-styrene (SEBS) in paraffin wax (PW). The C-C bond-enhanced OBC-SEBS networks synergistically improve the mechanical, thermal, and leakage-proof properties of PW@OBC-SEBS. Notably, the proposed peroxide-initiated chemical cross-linking method overcomes the limitations of conventional physical blending methods and thus can be applicable across diverse polymer matrices. We further demonstrate a portable and flexible PW@OBC-SEBS module that maintains a comfortable temperature range of 39-42 °C for personal thermotherapy. Our work provides a promising route to fabricate scalable polymer-based phase change composite for wearable thermal management.

Preparation and characterization of tannin-maltodextrin-polyvinyl alcohol hydrogel based on hydrogen bonding for wound healing.

The development of multifunctional and low-cost hydrogel dressings with good mechanical properties, antibacterial activity, and nontoxicity is of great relevance in healthcare. This study aimed to prepare a series of hydrogels consisting of maltodextrin (MD), polyvinyl alcohol (PVA), and tannic acid (TA) through a freeze-thaw cycling technique. Micro-acid hydrogels with different mass ratios (0, 0.25, 0.5, and 1 wt%) were obtained by adjusting the TA content. Among all hydrogels, TA-MP2 hydrogels (with a TA content of 0.5 wt%) showed good physicochemical and mechanical properties. In addition, the biocompatibility of TA-MP2 hydrogels was confirmed by the high cell survival rate of NIH3T3 cells, which was over 90% after 24 h and 48 h of incubation. Additionally, TA-MP2 hydrogels showed multifunctional properties, including antibacterial and antioxidative effects. In vivo experiments showed that TA-MP2 hydrogel dressings significantly accelerated wound healing in a full-layer skin wound model. These findings indicated the potential of TA-MP2 hydrogel dressings in promoting wound healing.

Construction of an individualized brain metabolic network in patients with advanced non-small cell lung cancer by the Kullback-Leibler divergence-based similarity method: A study based on 18F-fluorodeoxyglucose positron emission tomography.

Background: Lung cancer has one of the highest mortality rates of all cancers, and non-small cell lung cancer (NSCLC) accounts for the vast majority (about 85%) of lung cancers. Psychological and cognitive abnormalities are common in cancer patients, and cancer information can affect brain function and structure through various pathways. To observe abnormal brain function in NSCLC patients, the main purpose of this study was to construct an individualized metabolic brain network of patients with advanced NSCLC using the Kullback-Leibler divergence-based similarity (KLS) method. Methods: This study included 78 patients with pathologically proven advanced NSCLC and 60 healthy individuals, brain 18F-FDG PET images of these individuals were collected and all patients with advanced NSCLC were followed up (>1 year) to confirm their overall survival. FDG-PET images were subjected to individual KLS metabolic network construction and Graph theoretical analysis. According to the analysis results, a predictive model was constructed by machine learning to predict the overall survival of NSLCL patients, and the correlation with the real survival was calculated. Results: Significant differences in the degree and betweenness distributions of brain network nodes between the NSCLC and control groups (p<0.05) were found. Compared to the normal group, patients with advanced NSCLC showed abnormal brain network connections and nodes in the temporal lobe, frontal lobe, and limbic system. The prediction model constructed using the abnormal brain network as a feature predicted the overall survival time and the actual survival time fitting with statistical significance (r=0.42, p=0.012). Conclusions: An individualized brain metabolic network of patients with NSCLC was constructed using the KLS method, thereby providing more clinical information to guide further clinical treatment.