Advances in molecular basis of response to immunotherapy for penile cancer: better screening of responders.

Penile cancer is a rare malignant tumor of the male urinary system. The treatment benefit of standard first-line chemotherapy is not ideal for patients with locally advanced or metastatic lymph nodes. Immunotherapy has brought new treatment strategies and opportunities for patients with penile cancer. At present, clinical studies on immunotherapy for penile cancer have been reported, and the results show that it is effective but not conclusive. With the development of immunotherapy and the progress of molecular research technology, we can better screen the immunotherapy response population and explore new combination treatment regimens to evaluate the best combination regimen and obtain the optimal treatment options, which is also an important research direction for the immunotherapy of penile cancer in the future.

MiR-184-3p in the paraventricular nucleus participates in the neurobiology of depression via regulation of the hypothalamus-pituitary-adrenal axis.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis during chronic stress is essential for the pathogenesis of depression, and increased activity of cAMP response element binding protein (CREB)-regulated transcription co-activator 1 (CRTC1) in the paraventricular nucleus (PVN) plays a critical role. As a well-investigated microRNA (miRNA), miR-184 has two forms, miR-184-3p and miR-184-5p. Recently, miRNAs target genes predictive analysis and dual-luciferase reporter assays identified an inhibitory role of miR-184-3p on CRTC1 expression. Therefore, we speculated that miR-184-3p regulation was responsible for the effects of chronic stress on CRTC1 in the PVN. Various methods, including the chronic social defeat stress (CSDS) model of depression, behavioral tests, Western blotting, co-immunoprecipitation (Co-IP), quantitative real-time reverse transcription PCR (qRT-PCR), immunofluorescence, and adeno-associated virus (AAV)-mediated gene transfer, were used. CSDS evidently downregulated the level of miR-184-3p, but not miR-184-5p, in the PVN. Genetic knockdown and pharmacological inhibition of miR-184-3p in the PVN induced various depressive-like symptoms (e.g., abnormal behaviors, HPA hyperactivity, enhanced CRTC1 function in PVN neurons, downregulation of hippocampal neurogenesis, and decreased brain-derived neurotrophic factor (BDNF) signaling) in naïve male C57BL/6J mice. In contrast, genetic overexpression and pharmacological activation of miR-184-3p in the PVN produced significant beneficial effects against CSDS. MiR-184-3p in the PVN was necessary for the antidepressant actions of two well-known SSRIs, fluoxetine and paroxetine. Collectively. miR-184-3p was also implicated in the neurobiology of depression and may be a viable target for novel antidepressants.

[Effects of Landscape Pattern on Water Quality at Different Spatial and Temporal Scales in Wuding River Basin and Yanhe River Basin].

To explore the relationship between land use and water quality in basins with different land use patterns at different spatial and temporal scales, the Wuding River Basin and Yanhe River Basin were taken as research objects. Based on land use data in 2020 and water quality monitoring data during two periods, the redundancy analysis method was adopted to quantitatively explore the impact of land use on water quality at multiple scales. The results showed that： ① The main land use types in the two basins were cultivated land and grassland, and the difference was mainly in the proportion of bare land and forest land. ② The water quality in spring was better than that in autumn, and the water quality in the middle and lower reaches was worse. ③ The interpretation rate of land use on the riparian scale was the highest in the two basins. ④ The effect of land use on water quality was more significant in the Wuding River Basin in autumn than in spring, whereas the Yanhe River Basin showed the opposite trend. ⑤ Different land uses had different impacts on water quality. Bare land, cultivated land, and Shannon diversity index （SHDI） in the Wuding River Basin had significant impacts on water quality, whereas grassland, cultivated land, artificial surface, patch density （PD）, and SHDI were significant in the Yanhe River Basin. Cultivated land and artificial surfaces in the Wuding River Basin had a negative impact on water quality. Grassland and bare land had a negative correlation with most chemical indicators. Artificial surfaces and grasslands in the Yanhe River Basin had a negative impact on water quality, whereas forest land had a significant purification effect. The research results provide important information for sustainable land use and multi-scale landscape planning, which can be used to improve water quality.

Analysis of epidemiological characteristics of extrapulmonary tuberculosis from South-Central China.

Objectives: This study aimed to investigate the epidemiological and drug resistance (DR) characteristics of extrapulmonary tuberculosis (EPTB) in South-Central China. Methods: EPTB inpatients who were culture-positive for Mycobacterium tuberculosis were retrospectively included in a study at a provincial TB hospital in Hunan, a province in South-Central China, from January 2013 to December 2021. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment records. Descriptive statistical methods and a Chi-squared test were used to analyze the epidemiological and DR characteristics of EPTB patients. A logistic regression model was used to explore the risk factors of rifampicin-resistant/multidrug-resistant (RR/MDR)-EPTB. Results: A total of 1,324 cases were included. The majority of EPTB patients were in the age range of 20-29 years, were predominantly men (male-to-female ratio: 2.03), and were farmers (65.63%). Most EPTB cases were found in 2013 and 2017 from 2013 to 2021. The most prevalent subtypes of EPTB were lymphatic TB (29.83%, 395/1,324), multiple EPTB (20.85%, 276/1,324), and musculoskeletal TB (14.65%, 194/1,324). Musculoskeletal TB and genitourinary TB predominantly presented as exclusive EPTB forms, while lymphatic TB and pharyngeal/laryngeal TB often co-occurred with pulmonary TB (PTB). Drug susceptibility testing results showed that total DR rates (resistance to any of RFP, isoniazid [INH], streptomycin [STR], and/or ethambutol [EMB]) and RR/MDR rates in EPTB were 25.23% and 12.39%, respectively. Musculoskeletal TB exhibited the highest rates of total DR (31.40%), INH resistance (28.90%), STR resistance (20.10%), EMB resistance (6.20%), MDR (13.90%), and poly-DR (6.70%). The multivariable logistic regression model showed that patients aged from 20 to 59 years (compared to those aged 10 years), workers (compared to retirees), and EPTB patients from the south and west of Hunan (compared to those from the east of Hunan) were at an increased risk of developing RR/MDR EPTB (all OR values > 1). Conclusion: Our study provided a detailed account of the epidemiological and DR characteristics of EPTB in Hunan province, China. The significant DR rates, particularly in musculoskeletal TB cases, highlight the need for timely diagnosis, effective drug susceptibility testing, and the development of more effective treatment regimens for EPTB, especially targeting musculoskeletal TB treatments.

Unveiling an anoikis-related risk model and the role of RAD9A in colon cancer.

OBJECTIVE: Colorectal cancer (CRC), specifically colon adenocarcinoma, is the third most prevalent and the second most lethal form of cancer. Anoikis is found to be specialized form of programmed cell death (PCD), which plays a pivotal role in tumor progression. This study aimed to investigate the role of the anoikis related genes (ARGs) in colon cancer. METHODS: Consensus unsupervised clustering, differential expression analysis, tumor mutational burden analysis, and analysis of immune cell infiltration were utilized in the study. For the analysis of RNA sequences and clinical data of COAD patients, data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were obtained. A prognostic scoring system for overall survival (OS) prediction was developed using Cox regression and LASSO regression analysis. Furthermore, loss-of-function assay was utilized to explore the role of RAD9A played in the progression of colon cancer. RESULTS: The prognostic value of a risk score composed of NTRK2, EPHA2, RAD9A, CDC25C, and SNAI1 genes was significant. Furthermore, these findings suggested potential mechanisms that may influence prognosis, supporting the development of individualized treatment plans and management of patient outcomes. Further experiments confirmed that RAD9A could promote proliferation and metastasis of colon cancer cells. These effects may be achieved by affecting the phosphorylation of AKT. CONCLUSION: Differences in survival time and the tumor immune microenvironment (TIME) were observed between two gene clusters associated with ARGs. In addition, a prognostic risk model was established and confirmed as an independent risk factor. Furthermore, our data indicated that RAD9A promoted tumorigenicityby activating AKT in colon cancer.

Promoting Glutathione Synthesis: A Possibility for Treating Cardiomyopathy Induced by a Maternal Western Diet.

BACKGROUND: The adverse effects of a Western diet on obesity and diabetes among reproductive-aged women pose a significant threat to the cardiovascular health of their offspring. Given the crucial role of glutathione metabolism and glutathione-related antioxidant defense systems in cardiovascular diseases through scavenging ROS and maintaining redox homeostasis, further exploration of their specific influence is imperative to develop therapeutic strategies for cardiomyopathy induced by a maternal Western diet. METHODS: We developed a prenatal maternal Western diet exposure model in C57/B6 mice to investigate cardiac morphology and function through histological analysis and echocardiography. RNA sequencing and analysis were utilized to elucidate the mechanisms underlying the impact of a maternal Western diet and N-acetylcysteine treatment on cardiomyopathy. Additionally, ELISAs, transmission electron microscopy, and flow cytometry were employed to assess the antioxidant defense system and mitochondrial ROS levels in progenitor cardiomyocytes. RESULTS: N-acetylcysteine significantly mitigated cardiomyocyte hypertrophy, myocardial interstitial fibrosis, collagen type I accumulation, and left ventricular remodeling induced by a maternal Western diet, particularly in male offspring. Furthermore, N-acetylcysteine reversed the increase in apoptosis and the increase in the ß/α-MyHC ratio in the myocardium of offspring that results from a maternal Western diet. RNA sequencing and GSEA revealed that the beneficial effects of N-acetylcysteine were linked to its ability to modulate oxidative phosphorylation pathways. Additionally, N-acetylcysteine treatment during pregnancy can markedly elevate glutathione levels, augment glutathione peroxidase (GPx) activity, and mitigate the accumulation of mitochondrial ROS caused by a maternal Western diet. CONCLUSIONS: N-acetylcysteine mitigated cardiomyopathy induced by a maternal Western diet by bolstering glutathione synthesis and enhancing GPx activity, thereby scavenging mitochondrial ROS and modulating oxidative phosphorylation pathways.

Analysis on epidemiological and drug resistance characteristics of lymph node tuberculosis from Hunan province, China.

Objectives: To investigate the clinical epidemiological and drug resistance (DR) characteristics of lymph node tuberculosis (LNTB) in Hunan Province which locates in South-central China, and to provide scientific clues for effective prevention and treatment of LNTB. Methods: We retrospectively collected LNTB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital, the biggest TB reference hospital in South-central China, from January 2013 to December 2021. The multiple demographic, clinical and drug susceptibility data of patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. Results: Of the 577 LNTB cases, 373 (64.64%) were males, 352 (61.01%) were farmers; majority (161, 33.10%) aged at 20-29 years old; 147 (25.48%) had simple LNTB, 350 (60.66%) had LNTB combined with pulmonary TB (PTB) (defined as LNTB-PTB), and 80 (13.86%) had LNTB combined with other extrapulmonary TB (EPTB) (defined as LNTB-EPTB). A total of 345 (59.79%, 345/577) LNTB patients had cervical node infection, and the simple LNTB patients (81.63%, 120/147) had higher proportion of this infection than LNTB-PTB (51.71%, 181/350) and LNTB-EPTB (55.00%, 44/80) (both p values <0.017), respectively. LNTB-EPTB was more inclined to have abdominal tuberculous LNs (20%, 16/80) and at least four tuberculous lesions (22.50%, 18/80) than simple LNTB and LNTB-PTB. Seventy-seven (13.34%) and 119 (20.62%) were resistant to rifampicin (RIF) and isoniazid (INH), respectively; 72 (12.48%) were multi-drug resistant (MDR), and a total of 150 (26.00%) were DR (resistant to at least one of RIF, INH, ethambutol and streptomycin). LNTB patients aged 30-34 and 50-54 years old (compared to those aged <30 years) were independent predictors of RIF resistance (RR) (ORs were 3.47 and 2.83, respectively; 95% CIs were 1.64-7.35 and 1.08-7.46, respectively). Conclusion: Our study disclosed the epidemiological and DR characteristics of LNTB in Hunan Province, China. High LNTB prevalence was found in younger people while high RR LNTB prevalence was found in older ones, suggesting that we should conduct further studies to clarify the occurrence of RR in LNTB, meanwhile, strengthen the diagnoses and treatments of LNTB to prevent the emergence of RR.

Altered tumor microenvironment heterogeneity of penile cancer during progression from non-lymphatic to lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the major challenge in the treatment of penile cancer. The prognosis of individuals with lymphatic metastasis is extremely poor. Therefore, early identification of disease progression and lymphatic metastasis is an urgent task for researchers in penile cancer worldwide. METHODS: In this study, using single-cell RNA sequencing, an immune landscape was established for the cancer ecosystem based on 46,861 cells from six patients with penile cancer (four with lymphatic metastasis [stage IV] and two without lymphatic metastasis [stage I]). Using bulk RNA sequencing, the discrepancy between the cancers and their respective metastatic lymph nodes was depicted based on seven patients with penile cancer. RESULTS: The interaction between epithelial cells, fibroblasts, and endothelial cells, and the functional cooperation among invasion, epithelial-mesenchymal transition, and angiogenesis were found to be important landscapes in the penile cancer ecosystem, playing important roles in progression of cancer and lymph node metastasis. CONCLUSIONS: This study is the first to investigate the altered tumor microenvironment heterogeneity of penile cancer as it evolves from non-lymphatic to lymphatic metastasis and provides insights into the mechanisms underlying malignant progression, the premetastatic niche, and lymphatic metastasis in penile cancer.

Associations of muscle mass, strength, and quality with diabetes and the mediating role of inflammation in two National surveys from China and the United states.

AIMS: The evidence for joint and independent associations of low muscle mass and low muscle strength with diabetes is limited and mixed. The study aimed to determine the associations of muscle parameters (muscle mass, strength, quality, and sarcopenia) and sarcopenia obesity with diabetes, and the previously unstudied mediating effect of inflammation. MATERIALS AND METHODS: A total of 13,420 adults from the 2023 China National Health Survey (CNHS) and 5,380 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were included in this study. Muscle mass was determined using bioelectrical impedance analysis (BIA) in the CNHS, and whole-body dual X-ray absorptiometry (DXA) in the NHANES. Muscle strength was assessed using digital hand dynamometer. Multivariate logistic regression models were used to evaluate the associations of muscle parameters and sarcopenia obesity with diabetes. Inflammatory status was assessed using blood cell counts and two systemic inflammation indices (platelet-to-lymphocyte ratio (PLR) and system inflammation response index (SIRI)). Mediation analysis was conducted to examine inflammation's role in these associations. RESULTS: Low muscle mass and strength were independently related to diabetes. Low muscle quality was associated with elevated diabetes risk. Sarcopenia has a stronger association with diabetes compared to low muscle strength alone or mass alone (CNHS, odds ratio (OR) = 1.93, 95 % confidence interval (CI):1.64-2.27; NHANES, OR = 3.80, 95 %CI:2.58-5.58). Participants with sarcopenia obesity exhibit a higher risk of diabetes than those with obesity or sarcopenia alone (CNHS, OR = 2.21, 95 %CI:1.72-2.84; NHANES, OR = 6.06, 95 %CI:3.64-10.08). Associations between muscle parameters and diabetes were partially mediated by inflammation (mediation proportion: 1.99 %-36.64 %, P < 0.05). CONCLUSION: Low muscle mass and muscle strength are independently or jointly associated with diabetes, and inflammation might be a potential mechanism underlying this association. Furthermore, the synergistic effects of sarcopenia and obesity could significantly increase diabetes risk.

Unexpected weakened formation of disinfection byproducts and enhanced production of halates by cupric oxide during chlorination of peptide-bound aspartic acid.

Under the condition that the residual chlorine is guaranteed, the biofilm still thrives in drinking water distribution systems through secreting a large number of extracellular polymeric substances (EPS), in which protein components are the primary precursor of disinfection byproducts (DBPs), mostly in the form of combined amino acids. The aim of this study is to investigate the action of CuO on the formation of halates (XO3-, ClO3- and BrO3-) and DBPs (trihalomethanes, THMs; haloacetonitriles, HANs) with aspartic acid tetrapeptide (TAsp) as protein surrogate. The presence of CuO promoted the self-decay rather than TAsp-induced decay of oxidants, resulting in an increase in XO3- yield and a decrease in DBPs yield. It was CuO-induced weaker production of cyanoacetic acid and 3-oxopropanoic acid that induced the decreased yields of HANs and THMs, respectively. The FTIR and Raman spectra indicate a weak complexation between CuO and TAsp. Given this, the CuO-HOX/OX- complexes were inferred to be reactive to HOX/OX- but less reactive to TAsp. The study helps to better understand the formation of XO3- and DBPs during the chlorination of EPS, and propose precise control strategies when biofilm boosts in water pipes.

A novel pathogenic species of genus Stenotrophomonas: Stenotrophomonas pigmentata sp. nov.

Introduction: Stenotrophomonas is a prominent genus owing to its dual nature. Species of this genus have many applications in industry and agriculture as plant growth-promoting rhizobacteria and microbial biological control agents, whereas species such as Stenotrophomonas maltophilia are considered one of the leading gram-negative multi-drug-resistant bacterial pathogens because of their high contribution to the increase in crude mortality and significant clinical challenge. Pathogenic Stenotrophomonas species and most clinical isolates belong to the Stenotrophomonas maltophilia complex (SMc). However, a strain highly homologous to S. terrae was isolated from a patient with pulmonary tuberculosis (TB), which aroused our interest, as S. terrae belongs to a relatively distant clade from SMc and there have been no human association reports. Methods: The pathogenicity, immunological and biochemical characteristics of 610A2T were systematically evaluated. Results: 610A2T is a new species of genus Stenotrophomonas, which is named as Stenotrophomonas pigmentata sp. nov. for its obvious brown water-soluble pigment. 610A2T is pathogenic and caused significant weight loss, pulmonary congestion, and blood transmission in mice because it has multiple virulence factors, haemolysis, and strong biofilm formation abilities. In addition, the cytokine response induced by this strain was similar to that observed in patients with TB, and the strain was resistant to half of the anti-TB drugs. Conclusions: The pathogenicity of 610A2T may not be weaker than that of S. maltophilia. Its isolation extended the opportunistic pathogenic species to all 3 major clades of the genus Stenotrophomonas, indicating that the clinical importance of species of Stenotrophomonas other than S. maltophilia and potential risks to biological safety associated with the use of Stenotrophomonas require more attention.

Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study.

BACKGROUND: Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC). METHODS: TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance. RESULTS: The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003). CONCLUSIONS: The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.

Preoperative neoadjuvant targeted therapy remodels intra-tumoral heterogeneity of clear-cell renal cell carcinoma and ferroptosis inhibition induces resistance progression.

Neoadjuvant tyrosine kinase inhibitor (TKI) therapy is an important treatment option for advanced renal cell carcinoma (RCC). Many RCC patients may fail to respond or be resistant to TKI therapy. We aimed to explore the key mechanisms of neoadjuvant therapy résistance. We obtained tumor samples from matched pre-treatment biopsy and post-treatment surgical samples and performed single-cell RNA sequencing. Sunitinib-resistant ccRCC cell lines were established. Ferroptosis was detected by ferrous ion and lipid peroxidation levels. Tumor growth and resistance to Sunitinib was validated in vitro and vivo. Immunohistochemistry was used to validate the levels key genes and lipid peroxidation. Multi-center cohorts were included, including TCGA, ICGC, Checkmate-025 and IMmotion151 clinical trial. Survival analysis was performed to identify the associated clinical and genomic variables. Intratumoral heterogeneity was first described in the whole neoadjuvant management. The signature of endothelial cells was correlated with drug sensitivity and progression-free survival. Ferroptosis was shown to be the key biological program in malignant cell resistance. We observed tissue lipid peroxidation was negatively correlated with IL6 and tumor response. TKI-resistant cell line was established. SLC7A11 knockdown promoted cell growth and lipid peroxidation, increased the ferroptosis level, and suppressed the growth of tumor xenografts significantly (P < 0.01). IL6 could reverse the ferroptosis and malignant behavior caused by SLC7A11 (-) via JAK2/STAT3 pathway, which was rescued by the ferroptosis inducer Erastin. Our data indicate that ferroptosis is a novel strategy for advanced RCC treatment, which activated by IL6, providing a new idea for resistance to TKIs.

FOXD2-AS1 promotes malignant cell behavior in oral squamous cell carcinoma via the miR-378 g/CRABP2 axis.

BACKGROUND: Oral squamous cell cancer (OSCC) is a prevalent malignancy in oral cavity, accounting for nearly 90% of oral malignancies. It ranks sixth among the most common types of cancer worldwide and is responsible for approximately 145,000 deaths each year. It is widely accepted that noncoding RNAs participate cancer development in competitive regulatory interaction, knowing as competing endogenous RNA (ceRNA) network, whereby long non-coding RNA (lncRNA) function as decoys of microRNAs to regulate gene expression. LncRNA FOXD2-AS1 was reported to exert an oncogenic role in OSCC. Nevertheless, the ceRNA network mediated by FOXD2-AS1 was not investigated yet. This study aimed to explore the effect of FOXD2-AS1 on OSCC cell process and the underlying ceRNA mechanism. METHODS: FOXD2-AS1 expression in OSCC cells were determined via reverse transcription and quantitative polymerase chain reaction. Short hairpin RNA targeting FOXD2-AS1 was transfected into OSCC cells to silence FOXD2-AS1 expression. Then, loss-of-function experiments (n = 3 each assay) were performed to measure cell proliferation, apoptosis, migration, and invasion using colony formation, TdT-mediated dUTP Nick-End Labeling, wound healing and Transwell assays, respectively. RNA binding relation was verified by RNA immunoprecipitation and luciferase reporter assays. Rescue experiments were designed to validate whether FOXD2-AS1 affects cell behavior via the gene cellular retinoic acid binding protein 2 (CRABP2). Statistics were processed by GraphPad Prism 6.0 Software and SPSS software. RESULTS: FOXD2-AS1 was significantly upregulated in Cal27 and SCC9 cells (6.8 and 6.4 folds). In response to FOXD2-AS1 knockout, OSCC cell proliferation, migration and invasion were suppressed (approximately 50% decrease) while OSCC cell apoptosis was enhanced (more than two-fold increase). FOXD2-AS1 interacted with miR-378 g to alter CRABP2 expression. CRABP2 upregulation partly rescued (*p < 0.05, **p < 0.01, ***p < 0.001) the inhibitory impact of FOXD2-AS1 depletion on malignant characteristics of OSCC cells. CONCLUSION: FOXD2-AS1 enhances OSCC malignant cell behaviors by interacting with miR-378 g to regulate CRABP2 expression.

Smoking-induced CCNA2 expression promotes lung adenocarcinoma tumorigenesis by boosting AT2/AT2-like cell differentiation.

Lung adenocarcinoma (LUAD), a type of non-small cell lung cancer (NSCLC), originates from not only bronchial epithelial cells but also alveolar type 2 (AT2) cells, which could differentiate into AT2-like cells. AT2-like cells function as cancer stem cells (CSCs) of LUAD tumorigenesis to give rise to adenocarcinoma. However, the mechanism underlying AT2 cell differentiation into AT2-like cells in LUAD remains unknown. We analyze genes differentially expressed and genes with significantly different survival curves in LUAD, and the combination of these two analyses yields 147 differential genes, in which 14 differentially expressed genes were enriched in cell cycle pathway. We next analyze the protein levels of these genes in LUAD and find that Cyclin-A2 (CCNA2) is closely associated with LUAD tumorigenesis. Unexpectedly, high CCNA2 expression in LUAD is restrictedly associated with smoking and independent of other driver mutations. Single-cell sequencing analyses reveal that CCNA2 is predominantly involved in AT2-like cell differentiation, while inhibition of CCNA2 significantly reverses smoking-induced AT2-like cell differentiation. Mechanistically, CCNA2 binding to CDK2 phosphorylates the AXIN1 complex, which in turn induces ubiquitination-dependent degradation of ß-catenin and inhibits the WNT signaling pathway, thereby failing AT2 cell maintenance. These results uncover smoking-induced CCNA2 overexpression and subsequent WNT/ß-catenin signaling inactivation as a hitherto uncharacterized mechanism controlling AT2 cell differentiation and LUAD tumorigenesis.

The Role of JAK-STAT-SOCS1 Axis in Tumorigenesis, Malignant Progression and Lymphatic Metastasis of Penile Cancer.

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.

Fast and Massive Pixel-Level Morphology Detection by Imaging Processing for Inkjet Printing.

With the rapid development of the emerging intelligent, flexible, transparent, and wearable electronic devices, such as quantum-dot-based micro light-emitting diodes (micro-LEDs), thin-film transistors (TFTs), and flexible sensors, numerous pixel-level printing technologies have emerged. Among them, inkjet printing has proven to be a useful and effective tool for consistently printing micron-level ink droplets, for instance, smaller than 50 µm, onto wearable electronic devices. However, quickly and accurately determining the printing quality, which is significant for the electronic device performance, is challenging due to the large quantity and micron size of ink droplets. Therefore, leveraging existing image processing algorithms, we have developed an effective method and software for quickly detecting the morphology of printed inks served in inkjet printing. This method is based on the edge detection technology. We believe this method can greatly meet the increasing demands for quick evaluation of print quality in inkjet printing.

The simultaneous removal of methylene blue (MB) and Ca2+ by recyclable adsorbents based the scales derived from coal gasification system.

The transformation of solid wastes from industrial production into effective adsorbents could significantly contribute to wastewater treatment. In this study, after acidizing and burning soft scale (SS) from coal gasification system, two magnetic adsorbents (mag-ASS and mag-BASS) were prepared via the combination of magnetite with ultrasonic, respectively. The treatment effects of mag-ASS and mag-BASS were then investigated for simulated wastewater containing macromolecular organic matter [i.e., methylene blue (MB)] and Ca2+. The results indicated that the pseudo second order kinetic, Elovich, Freundlich, Langmuir and Temkin model could well describe the adsorption behavior of MB and Ca2+ onto mag-ASS and mag-BASS. The maximum adsorption capacities of mag-ASS for MB and mag-BASS for Ca2+ were 600.53 mg/g and 102.54 mg/g, respectively. Surprisingly, the adsorption abilities of mag-ASS for MB and mag-BASS for Ca2+ show significantly higher than the others. The adsorption mechanisms of MB mainly included electrostatic interaction, π-π conjugate interaction and cation exchange, while those of Ca2+ were mainly electrostatic interaction and cation exchange. The diffusion of MB and Ca2+ onto the magnetic adsorbents might be controlled by the combined effects of intraparticle and liquid film diffusion. There was no significant reduction in adsorption capacity after 8 cycles of adsorption and desorption, indicating that SS-based magnetic adsorbents had good recyclability and stability. Moreover, the removal efficiency of mag-BASS for total hardness and total organic carbon in real coal gasification gray water (CGGW) was 82.60 and 64.10%, respectively. The treatment of CGGW and the resource of wastes would significantly promote the reasonable disposal of coal gasification scales.

Photoregulatory protein kinases fine-tune plant photomorphogenesis by directing a bifunctional phospho-code on HY5 in Arabidopsis.

Photomorphogenesis is a light-dependent plant growth and development program. As the core regulator of photomorphogenesis, ELONGATED HYPOCOTYL 5 (HY5) is affected by dynamic changes in its transcriptional activity and protein stability; however, little is known about the mediators of these processes. Here, we identified PHOTOREGULATORY PROTEIN KINASE 1 (PPK1), which interacts with and phosphorylates HY5 in Arabidopsis, as one such mediator. The phosphorylation of HY5 by PPK1 is essential to establish high-affinity binding with B-BOX PROTEIN 24 (BBX24) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), which inhibit the transcriptional activity and promote the degradation of HY5, respectively. As such, PPKs regulate not only the binding of HY5 to its target genes under light conditions but also HY5 degradation when plants are transferred from light to dark. Our data identify a PPK-mediated phospho-code on HY5 that integrates the molecular mechanisms underlying the regulation of HY5 to precisely control plant photomorphogenesis.

Evaluation of water ecological health of Yanhe River based on benthic fauna integrity index.

Yanhe River Basin is located in the hilly gully area of the Loess Plateau with serious soil erosion. Strong human activities in the middle and lower reaches lead to fragile ecological environment. Soil erosion status varies among different geomorphic units within the watershed (loess liang hilly and gully region, loess mao hilly and gully region, and broken platform region). In this study, we surveyed the benthic community from the Yanhe River Basin in April (spring) and October (autumn) of 2021. To evaluate the water ecological health status of the watershed and investigate the effects of different geomorphic units on the benthic integrity of the benthos, we constructed the benthic-index of biotical integrity (B-IBI) based on the biological data. We identified a total of 113 species of 73 genera in 4 phyla of benthic fauna, with aquatic insects as the dominant taxa in both seasons. Through screening 26 candidate indicators, we found that the spring B-IBI consisted of three indicators: relative abundance of individuals of dominant taxonomic units, family biotic index (FBI), and relative abundance of predator individuals, and that autumn B-IBI was composed of the number of taxonomic units of Ephemeroptera, FBI value, and the relative abundance of predator individuals. Results of the B-IBI evaluation showed that 83.3% of the sampling sites in the upper mainstem and tributaries were at a healthy condition, while only 28.6% sampling sites in the middle and lower mainstem and tributaries were at a healthy condition. In addition, the health status of the watershed was better in spring than in autumn. The Kruskal-Wallis nonparametric tests showed that benthic density, species number, and B-IBI percentile scores in the fragmented loess area were significantly higher in spring than in autumn, and significantly lower in autumn than in the loess liang hilly and gully region and loess mao hilly and gully region, being mainly caused by the increasing erosion due to the concentrated rainfall in wet season. Results of the redundancy analysis showed that key environmental factors affecting benthic community structure in spring were boulder substrate, chlorophyll-a, oxidation reduction potential, turbidity, conductivity, and dissolved oxygen, and were nitrate-nitrogen, oxidation reduction potential, and pH in autumn.