DCAF13 promotes ovarian cancer progression by activating FRAS1-mediated FAK signaling pathway.

Cullin-RING ubiquitin ligase 4 (CRL4) is closely correlated with the incidence and progression of ovarian cancer. DDB1- and CUL4-associated factor 13 (DCAF13), a substrate-recognition protein in the CRL4 E3 ubiquitin ligase complex, is involved in the occurrence and development of ovarian cancer. However, its precise function and the underlying molecular mechanism in this disease remain unclear. In this study, we confirmed that DCAF13 is highly expressed in human ovarian cancer and its expression is negatively correlated with the overall survival rate of patients with ovarian cancer. We then used CRISPR/Cas9 to knockout DCAF13 and found that its deletion significantly inhibited the proliferation, colony formation, and migration of human ovarian cancer cells. In addition, DCAF13 deficiency inhibited tumor proliferation in nude mice. Mechanistically, CRL4-DCAF13 targeted Fraser extracellular matrix complex subunit 1 (FRAS1) for polyubiquitination and proteasomal degradation. FRAS1 influenced the proliferation and migration of ovarian cancer cell through induction of the focal adhesion kinase (FAK) signaling pathway. These findings collectively show that DCAF13 is an important oncogene that promotes tumorigenesis in ovarian cancer cells by mediating FRAS1/FAK signaling. Our findings provide a foundation for the development of targeted therapeutics for ovarian cancer.

Trace elements in the Upper Indus River Basin (UIRB) of Western Himalayas: Quantification, sources modeling, and impacts.

This study conducted a comprehensive analysis of trace element concentrations in the Upper Indus River Basin (UIRB), a glacier-fed region in the Western Himalayas (WH), aiming to discern their environmental and anthropogenic sources and implications. Despite limited prior data, 69 samples were collected in 2019 from diverse sources within the UIRB, including mainstream, tributaries, and groundwater, to assess trace element concentrations. Enrichment factor (EF) results and comparisons with regional and global averages suggest that rising levels of Zn, Cd, and As may pose safety concerns for drinking water quality. Advanced multivariate statistical techniques such as principal component analysis (PCA), absolute principal component scores (APCS-MLR), Monte Carlo simulation (MCS), etc were applied to estimate the associated human health hazards and also identified key sources of trace elements. The 95th percentile of the MCS results indicates that the estimated total cancer risk for children is significantly greater than (>1000 times) the USEPA's acceptable risk threshold of 1.0 × 10-6. The results classified most of the trace elements into two distinct groups: Group A (Li, Rb, Sr, U, Cs, V, Ni, TI, Sb, Mo, Ge), linked to geogenic sources, showed lower concentrations in the lower-middle river reaches, including tributaries and downstream regions. Group B (Pb, Nb, Cr, Zn, Be, Al, Th, Ga, Cu, Co), influenced by both geogenic and anthropogenic activities, exhibited higher concentrations near urban centers and midstream areas, aligning with increased municipal waste and agricultural activities. Furthermore, APCS-MLR source apportionment indicated that trace elements originated from natural geogenic processes, including rock-water interactions and mineral dissolution, as well as anthropogenic activities. These findings underscore the need for targeted measures to mitigate anthropogenic impacts and safeguard water resources for communities along the IRB and WH.

TRIM38 Induced in Respiratory Syncytial Virus-infected Cells Downregulates Type I Interferon Expression by Competing with TRIM25 to Bind RIG-I.

Innate immune response is the first line of defense for the host against virus invasion. One important response is the synthesis and secretion of type I interferon (IFN-I) in the virus-infected host cells. Here, we found that respiratory syncytial virus (RSV) infection induced high expression of TRIM25, which belongs to the tripartite motif-containing (TRIM) family of proteins. TRIM25 bound and activated retinoic acid-inducible gene I (RIG-I) by K63-linked ubiquitination. Accordingly, RIG-I mediated the production of IFN-I mainly through the nuclear factor kappa-B (NF-κB) pathway in respiratory epithelial cells. Interestingly, IFN-I, in turn, promoted a high expression of TRIM38 which downregulated the expression of IFN-I by reducing the protein level of RIG-I by K48-linked ubiquitination. More importantly, the binding site of TRIM25 to RIG-I was found in the narrow 25th-43rd amino acid (aa) region of RIG-I N-terminus. In contrast, the binding sites of TRIM38 to RIG-I were found in a much wider amino acid region, which included the binding site of TRIM25 on RIG-I. As a result, TRIM38 inhibits the production of IFN-I by competing with TRIM25 for RIG-I binding. Thus, TRIM38 negatively regulates RIG-I activation to, in turn, downregulate IFN-I expression, thus interfering with host immune response. A negative feedback loop effectively "puts the brakes" on the reaction once host immune response is overactivated and homeostasis is unbalanced. We also discovered that TRIM25 bound RIG-I by a new K63-linked ubiquitination located at K-45 of the first caspase recruitment domain (CARD). Collectively, these results confirm an antagonism between TRIM38 and TRIM25 in regulating IFN-I production by affecting RIG-I activity following RNA virus infection.

Study on the oxidized gas production characteristics and spontaneous combustion tendency of pre-oxidized water-soaked coal in lean-oxygen environments.

The oxidation characteristics and spontaneous combustion (SC) tendency of raw long-flame coal (RC), water-soaked 200-day coal (S200), pre-oxidized water-soaked coal at 200 °C (O200S200), and pre-oxidized soaked coal at 300 °C (O300S200) in an oxygen-poor environment were investigated using a programmed warming system. The results show that pre-oxidation water-soaked treatment (PWT) promotes the coal-oxygen complex reaction and increases the rate of coal oxygen consumption (OCR) and the rate of carbon and oxygen compound production. The rate of CO and CO2 production of the water-soaked (WS) coal increased by 0.329 mol·(cm3·s)-1 and 0.922 mol·(cm3·s)-1, respectively, compared with that of the original coal sample. PWT reduces the activation energy of coal in the low-temperature oxidation stage (the maximum difference can be up to 110.99 kJ/mol) and enhances the oxidizing and heat-releasing capacity. There was a synergistic effect between the pre-oxidation (PO) and WS treatment, and the lowest comprehensive determination index of the SC propensity of coal in O200S200 samples was 831.92 which was 4.72 lower than that of RC samples, presenting a more SC tendency. Low oxygen concentration has an inhibitory effect on the oxidation characteristic parameters of coal, and the apparent activation energy of the low-temperature oxidation stage of pre-oxidized water-soaked coal (PWC) increased to 206.418 kJ/mol at 3% oxygen concentration. The lower the oxygen concentration of the anoxic environment, the lower the risk of SC of the coal samples. The results of the study can provide theoretical guidance for the identification and prevention of SC disasters in coal seams with shallow burial and close spacing.

Application of double-tube negative pressure drainage in repair of refractory wounds.

OBJECTIVE: To observe the application effect of double-tube negative pressure drainage in the repair of refractory wounds. METHODS: From January 2020 to April 2023, 50 patients undergoing refractory wound repair in the Department of Burn and Plastic Surgery of Jingjiang People's Hospital, Jiangsu were selected. According to different treatment methods, they were divided into an observation group and a control group, with 25 patients in each group. The observation group was treated with double-tube negative pressure drainage inside and outside the wound, while the control group was treated with negative pressure drainage inside the wound. By two-week observation, the wound healing status and complication rate after treatment, as well as the wound bacterial clearance rate, wound pain score and patient satisfaction 3, 7 and 14 d after treatment were compared between the two groups. Statistical analysis was carried out to determine the efficacy. RESULTS: After treatment for two weeks, the observation group showed a higher grade A healing rate (92% vs. 60%, X2  = 7.018, P = 0.008), a higher wound bacterial clearance rate (100% vs. 76%, X2  = 6.818, P = 0.03), a lower pain score (1.44 ± 0.51 vs. 2.36 ± 0.49, t = -6.53, P < 0.01), a higher patient satisfaction score (8.48 ± 0.96 vs. 6.64 ± 0.95, t = 6.80, P < 0.01), and a lower complication rate (8% vs. 40%, X2 = 7.018, P = 0.008) compared with the control group. CONCLUSION: Double-tube negative pressure drainage has a significant application effect in the repair of refractory wounds. It can accelerate wound healing, shorten treatment time, effectively eliminate bacteria, relieve wound infection, reduce complications, alleviate pain and improve patient satisfaction. Therefore, the application, promotion and research of double-tube negative pressure drainage should be strengthened in clinical practice.

Dynamic Stiffening Hydrogel with Instructive Stiffening Timing Modulates Stem Cell Fate In Vitro and Enhances Bone Remodeling In Vivo.

Biomechanical stimuli derived from the extracellular matrix (ECM) extremely tune stem cell fate through 3D and spatiotemporal changes in vivo. The matrix stiffness is a crucial factor during bone tissue development. However, most in vitro models to study the osteogenesis of mesenchymal stem cells (MSCs) are static or stiffening in a 2D environment. Here, a dynamic and controllable stiffening 3D biomimetic model is created to regulate the osteogenic differentiation of MSCs with a dual-functional gelatin macromer that can generate a double-network hydrogel by sequential enzymatic and light-triggered crosslinking reactions. The findings show that these dynamic hydrogels allowed cells to spread and expand prior to the secondary crosslinking and to sense high stiffness after stiffening. The MSCs in the dynamic hydrogels, especially the hydrogel stiffened at the late period, present significantly elevated osteogenic ECM secretion, gene expression, and nuclear localization of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). In vivo evaluation of animal experiments further indicates that the enhancement of dynamic stiffening on osteogenesis of MSCs substantially promotes bone remodeling. Consequently, this work reveals that the 3D dynamic stiffening microenvironment as a critical biophysical cue not only mediates the stem cell fate in vitro, but also augments bone restoration in vivo.

Cbl induced ubiquitination of HER2 mediate immune escape from HER2-targeted CAR-T.

Breast cancer (BC) with high HER2 expression has higher recurrence rate and worse prognosis, and its immunotherapy is promising. Based on the high expression of HER2, develop Chimeric Antigen Receptor T-cell (CAR-T) and PDL-1 immunotherapy, and study the molecular pathways of related immune cells and recurrence. HER2-CAR-T cells were constructed using retroviruses, and their specific recognition and immune effects on HER2+ BC cells were verified by in vivo and in vitro experiments. PDL-1 was used as adjuvant immunotherapy, knocking down PDL-1 in tumor cells or dendritic cells, or depleted macrophages to study immune pathways. The negative regulation of HER2 by cbl was determined by IP, ubiquitination experiments, and segmented plasmids, elucidating the molecular mechanism of HER2+ BC recurrence after immunotherapy. HER2-CAR-T specifically recognizes HER2-positive tumor cells and inhibits tumor growth in vivo and in vitro, and anti-PDL1 treatment enhances the therapeutic effect of HER2-CAR-T on tumors. HER2-CART therapy eradicated solid tumors after PDL1 knockdown in dendritic cells. Immunotherapy of relapsed tumors lost HER2 expression by upregulating cbl. HER2-CAR-T shows specific recognition of HER2+ cells and can mediate immune response therapy with the cooperation of PDL-1.

Flexible aluminum-doped hafnium oxide ferroelectric synapse devices for neuromorphic computing.

The HfO2-based ferroelectric tunnel junction has received outstanding attention owing to its high-speed and low-power characteristics. In this work, aluminum-doped HfO2 (HfAlO) ferroelectric thin films are deposited on a muscovite substrate (Mica). We investigate the bending effect on the ferroelectric characteristics of the Au/Ti/HfAlO/Pt/Ti/Mica device. After 1000 bending times, the ferroelectric properties and the fatigue characteristics are largely degraded. The finite element analysis indicates that crack formation is the main reason for the fatigue damage under threshold bending diameters. Moreover, the HfAlO-based ferroelectric synaptic device exhibits excellent performance of neuromorphic computing. The artificial synapse can mimic the paired-pulse facilitation and long-term potentiation/depression of biological synapses. Meanwhile, the accuracy of digit recognition is 88.8%. This research provides a new research idea for the further development of hafnium-based ferroelectric devices.

Immune checkpoints expression patterns in early-stage triple-negative breast cancer predict prognosis and remodel the tumor immune microenvironment.

Background: Currently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown. Method: Herein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs). Results: Two ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group. Conclusion: Collectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.

One double-loaded suture anchor is sufficient for all-inside arthroscopic anterior talofibular ligament repair.

PURPOSE: All-inside anterior talofibular ligament (ATFL) repair using anchors is frequently used to manage chronic lateral ankle instability (CLAI) with satisfactory functional outcomes. It remains unclear whether there are differences in the functional results between the use of one or two double-loaded anchors. METHODS: This retrospective cohort study included 59 CLAI patients who underwent an all-inside arthroscopic ATFL repair procedure from 2017 to 2019. Patients were divided into two groups according to the number of anchors used. In the one-anchor group (n = 32), the ATFL was repaired with one double-loaded suture anchor. In the two-anchors group (n = 27), the ATFL was repaired with two double-loaded suture anchors. At the last follow-up time point, the Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Function Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports in both groups were compared. RESULTS: All the patients were followed up for at least 24 months. Improvement in the functional results (VAS, AOFAS, KAFS, ATT, and AJPS) were recorded at the final follow-up time point. No significant differences were observed regarding VAS, AOFAS, KAFS, ATT, and AJPS between the two groups. CONCLUSION: In patients with CLAI undergoing all-inside arthroscopic ATFL repair, the use of either one or two double-loaded suture anchors produces comparable and predictably good functional outcomes. LEVEL OF EVIDENCE: Level III.

Cellular Prion Protein Attenuates OGD/R-Induced Damage by Skewing Microglia toward an Anti-inflammatory State via Enhanced and Prolonged Activation of Autophagy.

Modulation of microglial pro/anti-inflammatory states and autophagy are promising new therapies for ischemic stroke, but the underlying mechanisms remain largely unexplored. The objective of the study is to determine the intrinsic role of PrPC (cellular prion protein) in the regulation of microglial inflammatory states and autophagy in ischemic stroke. PrPC was expressed in murine microglia, and an in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established in microglia of different PRNP genotypes. During reperfusion following OGD, wild-type (WT) microglia had significantly increased pro/anti-inflammatory microglial percentages and related cytokine [interleukin [IL]-6, IL-10, IL-4, tumor necrosis factor, and interferon-gamma] release at reperfusion after 48 or 72 h. WT microglia also showed greater accumulation of the autophagy markers LC3B-II/I (microtubule-associated protein B-light chain 3), but not of p62 or LAMP1 (lysosome-associated membrane protein) at reperfusion after 24 h and 48 h. Inhibition of autophagy using 3-methyladenine or bafilomycin A1 aggravated the OGD/R-induced pro-inflammatory state, and the effect of 3-methyladenine was significantly stronger than that of bafilomycin A1. Concomitantly, PRNP knockout shortened the accumulation of LC3B-II/I, suppressed microglial anti-inflammatory states, and further aggravated the pro-inflammatory states. Conversely, PRNP overexpression had the opposite effects. Bafilomycin A1 reversed the effect of PrPC on microglial inflammatory state transformation. Moreover, microglia with PRNP overexpression exhibited higher levels of LAMP1 expression in the control and OGD/R groups and delayed the OGD/R-induced decrease of LAMP1 to reperfusion after 48 h. PrPC attenuates OGD/R-induced damage by skewing microglia toward an anti-inflammatory state via enhanced and prolonged activation of autophagy.

Case report: Excessive daytime sleepiness as a presenting manifestation of autoimmune glial fibrillary acidic protein astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a recently discovered autoimmune inflammatory disease of the central nervous system. It presents with a variety of clinical symptoms, including fever, seizures, psychiatric symptoms, limber weakness, and sensory symptoms. However, the symptoms of sleep disorders have not been sufficiently addressed. Here, we report a case of GFAP-A in which the patient complained of excessive daytime sleepiness and an excessive need for sleep. Our patient was a 58-year-old male who experienced excessive daytime sleepiness for 50 days following SARS-CoV-2 infection. He was diagnosed with coronavirus disease 2019 on June 1st. On the 7th of June, he experienced excessive daytime sleepiness, nausea, reduced food intake, lower limb weakness, and dysuria. Subsequently, his sleepiness significantly deteriorated on July 21st. Five months prior, the patient underwent laparoscopic partial right nephrectomy for clear-cell renal cell carcinoma. Brain MRI revealed abnormal hyperintense lesions in the pontine brain and around the mesencephalic aqueduct on T2 and T2-fluid attenuated inversion recovery (T2-FLAIR) sequences However, these lesions did not exhibit any pathological enhancement. Spinal cord MRI revealed lesions in the C6-C7 and T2-T3 segments on the T2 sequence. His Epworth Sleepiness Scale (ESS) score was 16 (reference range, <10), and 24-hour polysomnography supported the diagnosis of rapid-eye-movement sleep disorder and severe sleep apnea-hypopnea syndrome. Glial fibrillary acidic protein IgG antibodies were detected in the cerebrospinal fluid (1:32, cell-based assay) but not in the serum. The level of hypocretin in the cerebrospinal fluid was 29.92 pg/mL (reference range ≥110 pg/mL), suggesting narcolepsy type 1. After treatment with corticosteroids for approximately 1 month, the patient showed considerable clinical and radiological improvement, as well as an increase in hypocretin levels. Although repeated polysomnography and multiple sleep latency tests suggested narcolepsy, his ESS score decreased to 8. Our findings broaden the range of clinical manifestations associated with GFAP-A, thereby enhancing diagnostic and therapeutic strategies for this disease. Additionally, our results indicate a potential common autoimmune mechanism involving GFAP-A and orexin system dysregulation, warranting further investigation.

Systematic Investigation of the Multifaceted Role of SOX11 in Cancer.

SRY-box transcription factor 11 (SOX11), as a member of the SOX family, is a transcription factor involved in the regulation of specific biological processes and has recently been found to be a prognostic marker for certain cancers. However, the roles of SOX11 in cancer remain controversial. Our study aimed to explore the various aspects of SOX11 in pan-cancer. The expression of SOX11 was investigated by the Genotype Tissue-Expression (GTEX) dataset and the Cancer Genome Atlas (TCGA) database. The protein level of SOX11 in tumor tissues and tumor-adjacent tissues was verified by human pan-cancer tissue microarray. Additionally, we used TCGA pan-cancer data to analyze the correlations among SOX11 expression and survival outcomes, clinical features, stemness, microsatellite instability (MSI), tumor mutation burden (TMB), mismatch repair (MMR) related genes and the tumor immune microenvironment. Furthermore, the cBioPortal database was applied to investigate the gene alterations of SOX11. The main biological processes of SOX11 in cancers were analyzed by Gene Set Enrichment Analysis (GSEA). As a result, aberrant expression of SOX11 has been implicated in 27 kinds of cancer types. Aberrant SOX11 expression was closely associated with survival outcomes, stage, tumor recurrence, MSI, TMB and MMR-related genes. In addition, the most frequent alteration of the SOX11 genome was mutation. Our study also showed the correlations of SOX11 with the level of immune infiltration in various cancers. In summary, our findings underline the multifaceted role and prognostic value of SOX11 in pan-cancer.

Functional outcomes of all-inside arthroscopic anterior talofibular ligament repair with loop suture versus free-edge suture.

BACKGROUND: Anatomic repair of anterior talofibular ligament (ATFL) is used to manage chronic lateral ankle instability (CLAI). However, the optimal suture configuration used to repair the ATFL is not yet determined. It remains unclear whether suture configuration affects clinical outcomes in such patients. PURPOSE: To compare the functional outcomes of all-inside arthroscopic ATFL repair using either a loop suture and or a free-edge suture configuration in CLAI patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included 71 patients with CLAI who had undergone an all-inside arthroscopic ATFL repair procedure with either loop suture (n = 36) or free-edge suture (n = 35) from February 2016 to July 2018. Comparable pre-operatively, the Visual analogy score (VAS), American Orthopedic Foot and Ankle Society scoring system (AOFAS), Karlsson Ankle Functional Score (KAFS) scoring system, Anterior Talar Translation (ATT) and Active Joint Position Sense (AJPS) were used to evaluate postoperative ankle function. RESULTS: There were no postoperative wound complications, implant reactions, or neurological or vascular injuries. Postoperative hospitalization, VAS, AOFAS, KAFS, AJPS and the time of return to sport were similar between the loop suture group and free-edge suture group. Requiring a longer procedure time, patients with loop suture configuration achieved better ATT. CONCLUSION: All-inside arthroscopic ATFL repair procedure for CLAI treatment provides better ATT and comparable functional outcomes when a loop suture configuration is used instead of a free-edge suture configuration. A statistical difference in ATT was observed. Given the relatively short follow-up, it is questionable whether this will have any clinical relevance.

Combination of Immune-Related Network and Molecular Typing Analysis Defines a Three-Gene Signature for Predicting Prognosis of Triple-Negative Breast Cancer.

Recent breakthroughs in immune checkpoint inhibitors (ICIs) have shown promise in triple-negative breast cancer (TNBC). Due to the intrinsic heterogeneity among TNBC, clinical response to ICIs varies greatly among individuals. Thus, discovering rational biomarkers to select susceptible patients for ICIs treatment is warranted. A total of 422 TNBC patients derived from The Cancer Genome Atlas (TCGA) database and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were included in this study. High immunogenic gene modules were identified using weighted gene co-expression network analysis (WGCNA). Immune-related genes (IRGs) expression patterns were generated by consensus clustering. We developed a three-gene signature named immune-related gene panel (IRGP) by Cox regression method. Afterward, the associations of IRGP with survival outcomes, infiltration of immune cells, drug sensitivity, and the response to ICIs therapy were further explored. We found five high immunogenic gene modules. Two distinct IRGclusters and IRG-related genomic clusters were identified. The IRGP was constructed based on TAPBPL, FBP1, and GPRC5C genes. TNBC patients were then subdivided into high- and low-IRGriskscore subgroups. TNBC patients with low IRGriskscore had a better survival outcome, higher infiltration of immune cells, lower TP53 mutation rate, and more benefit from ICIs treatment than high IRGriskscore patients. These findings offer novel insights into molecular subtype of TNBC and provided potential indicators for guiding ICIs treatment.

Gate-Modulated High-Response Field-Effect Transistor-Type Gas Sensor Based on the MoS2/Metal-Organic Framework Heterostructure.

The high surface-to-volume ratio and decent material properties of two-dimensional (2D) transition metal dichalcogenides (TMDs) make them advantageous as an active channel in field-effect transistor (FET)-type gas sensing devices. However, most existing TMD gas sensors are based on a two-terminal resistance-type structure and suffer from low responsivity and slow response, which has urged materials optimization as well as device engineering. Metal-organic frameworks (MOFs) have a large number of ordered binding sites in the pores that can specifically bind to gas molecules and can be decorated on TMD surfaces to enhance gas sensing capabilities. In this work, we successfully realize the FET-type gas sensor with MoS2-MOF as the channel. The fabricated gas sensor exhibits enhanced NH3 sensing performance (22.475 times higher in responsivity) as compared to the device with a bare MoS2 channel. In addition, the FET-type gas sensor geometry enables effective tuning of sensitivity through electrical gating based on the modulation over the channel carrier concentration. Furthermore, the dependence of responsivity on the MoS2 thickness is investigated as well to achieve an in-depth understanding of the electrical modulation mechanism of the MOF-decorated MoS2 gas sensors. The demonstrated results can pave an attractive pathway toward the realization of advanced high-response and tunable TMD-based gas sensing devices.

Exploring potential targets of Actinidia chinensis Planch root against hepatocellular carcinoma based on network pharmacology and molecular docking and development and verification of immune-associated prognosis features for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the malignant tumors with the highest morbidity and mortality worldwide, and its prognosis remains a challenge. Actinidia chinensis Planch (ACP) root has good efficacy against HCC. This study aimed to explore the link between ACP and potential targets of HCC, and to develop a novel immune-based gene signature to predict HCC patient survival. Methods: Transcriptome data and clinical information on HCC were obtained from The Cancer Genome Atlas (TCGA; HCC: 374, normal: 50) and International Cancer Genome Consortium (ICGC) database (HCC: 243, normal: 202). Combined with the 2,483 immune-related genes from the Immport database, we used the least absolute shrinkage and selection operator (LASSO) to construct a prognostic model. Patients were divided into high-risk and low-risk groups by the median of the risk scores of the TCGA cohort. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves were used to estimate the predictability of the model in HCC prognosis, and carried out external validation based on ICGC cohort. We analyzed the correlation of this model with immune cells and immune checkpoint genes. Finally, molecular docking of these genes and the corresponding ACP components. Results: We constructed a prognostic model composed of 3 immune-related genes [epidermal growth factor (EGF), baculoviral inhibitor of apoptosis repeat-containing protein 5 (BIRC5), and secreted phosphoprotein 1 (SPP1)]. And the high-risk group had a lower overall survival (OS) rate compared to the low-risk group (TCGA cohort: P=1.761e-05, ICGC cohort: P=8.716e-04). The outcomes of the AUC of ROC of prognostic risk model to predict for 1-, 2-, and 3-year OS: TCGA cohort: 0.749, 0.710, and 0.653 and ICGC cohort: 0.698, 0.736, and 0.753. Molecular docking results showed that quercetin had good binding activities with SPP1, BIRC5, and EGF, and ursolic acid (UA) and BIRC5 also had this feature. Conclusions: Our study speculates that ACP root anti-HCC may be involved in the immune regulation of the body by targeting EGF, BIRC5 and SPP1, which possess great potential and value as early warning molecules for HCC. This model may provide a reference for individualized diagnosis and treatment for HCC patients.

Gas sensing devices based on two-dimensional materials: a review.

Gas sensors have been widely utilized penetrating every aspect of our daily lives, such as medical industry, environmental safety testing, and the food industry. In recent years, two-dimensional (2D) materials have shown promising potential and prominent advantages in gas sensing technology, due to their unique physical and chemical properties. In addition, the ultra-high surface-to-volume ratio and surface activity of the 2D materials with atomic-level thickness enables enhanced absorption and sensitivity. Till now, different gas sensing techniques have been developed to further boost the performance of 2D materials-based gas sensors, such as various surface functionalization and Van der Waals heterojunction formation. In this article, a comprehensive review of advanced gas sensing devices is provided based on 2D materials, focusing on two sensing principles of charge-exchange and surface oxygen ion adsorption. Six types of typical gas sensor devices based on 2D materials are introduced with discussion of latest research progress and future perspectives.

Self-Organizing, Environmentally Stable, and Low-Cost Copper-Nickel Complex Inks for Printed Flexible Electronics.

Cost-effective copper conductive inks are considered as the most promising alternative to expensive silver conductive inks for use in printed electronics. However, the low stability and high sintering temperature of copper inks hinder their practical application. Herein, we develop rapidly customizable and stable copper-nickel complex inks that can be transformed in situ into uniform copper@nickel core-shell nanostructures by a self-organized process during low-temperature annealing and immediately sintered under photon irradiation to form copper-nickel alloy patterns on flexible substrates. The complex inks are synthesized within 15 min via a simple mixing process and are particle-free, air-stable, and compatible with large-area screen printing. The manufactured patterns exhibit a high conductivity of 19-67 µΩ·cm, with the value depending on the nickel content, and can maintain high oxidation resistance at 180 °C even when the nickel content is as low as 6 wt %. In addition, the printed copper-nickel alloy patterns exhibit high flexibility as a consequence of the local softening and mechanical anchoring effect between the metal pattern and the flexible substrate, showing strong potential in the additive manufacturing of highly reliable flexible electronics, such as flexible radio-frequency identification (RFID) tags and various wearable sensors.

Clinical Significance and Prognostic Value of Human Soluble Resistance-Related Calcium-Binding Protein: A Pan-Cancer Analysis.

The soluble resistance-related calcium-binding protein (sorcin, SRI) serves as the calcium-binding protein for the regulation of calcium homeostasis and multidrug resistance. Although the mounting evidence suggests a crucial role of SRI in the chemotherapeutic resistance of certain types of tumors, insights into pan-cancer analysis of SRI are unavailable. Therefore, this study aimed to probe the multifaceted properties of SRI across the 33 cancer types. The SRI expression was analyzed via The Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEX) database. The SRI genomic alterations and drug sensitivity analysis were performed based on the cBioPortal and the CellMiner database. Furthermore, the correlations among the SRI expression and survival outcomes, clinical features, stemness, tumor mutation burden (TMB), microsatellite instability (MSI), and immune cells infiltration were analyzed using TCGA data. The differential analysis showed that SRI was upregulated in 25 tumor types compared with the normal tissues. Aberrant expression of SRI was able to predict survival in different cancers. Further, the most frequent alteration of SRI genomic was amplification. Moreover, the aberrant SRI expression was related to stemness score, epithelial-mesenchymal-transition (EMT)-related genes, MSI, TMB, and tumor immune microenvironment in various types of cancer. TIMER database mining further found that the SRI expression was significantly correlated with the infiltration levels of various immune cells in certain types of cancer. Intriguingly, the SRI expression was negatively correlated with drug sensitivity of fluorouracil, paclitaxel, docetaxel, and isotretinoin. Our findings highlight the predictive value of SRI in cancer and provide insights for illustrating the role of SRI in tumorigenesis and drug resistance.