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Upon injury, nearby cells, including fibroblasts at the wound edge, are often found in a hypoxic microenvironment. Nevertheless, the influence of hypoxia on skin fibroblasts is poorly understood. Using previously established mouse full‐thickness wounds, we show that Bcl‐2 and adenovirus E1B 19‐kDa interacting protein 3 (BNIP3) expression was significantly elevated at the wound edge, and hypoxia treatment enhanced BNIP3 expression in fibroblasts. Interestingly, BNIP3 promoted the migration and proliferation, as well as the activation of autophagy, in fibroblasts under hypoxia. The hypoxia‐induced autophagy was found to induce the migration and proliferation of fibroblasts, a process that could be reversed by knocking down the autophagy‐related gene for autophagy protein 5, ATG5. Furthermore, hypoxia‐inducible factor 1 subunit alpha (HIF‐1α) was significantly upregulated in fibroblasts under hypoxia treatment, and HIF‐1α knockdown attenuated the hypoxia‐induced expression of BNIP3 and the migration and proliferation of fibroblasts. Altogether, our results establish the hypoxia‐BNIP3‐autophagy signaling axis as a newly identified regulatory mechanism of skin fibroblast migration and proliferation upon wounding. Autophagy intervening might thus represent a promising therapeutic strategy for patients with chronic refractory wounds. [ABSTRACT FROM AUTHOR]

Monkeypox was declared a global health emergency by the World Health Organization, and as of March 2023, 86,000 confirmed cases and 111 deaths across 110 countries have been reported. Its causal agent, monkeypox virus (MPV) belongs to a large family of double-stranded DNA viruses, Orthopoxviridae, that also includes vaccinia virus (VACV) and others. MPV produces two distinct forms of viral particles during its replication cycles: the enveloped viron (EV) that is released via exocytosis, and the mature viron (MV) that is discharged through lysis of host cells. This study was designed to develop multi-valent mRNA vaccines against monkeypox EV and MV surface proteins, and examine their efficacy and mechanism of action. Four mRNA vaccines were produced with different combinations of surface proteins from EV (A35R and B6R), MV (A29L, E8L, H3L and M1R), or EV and MV, and were administered in Balb/c mice to assess their immunogenicity potentials. A dynamic immune response was observed as soon as seven days after initial immunization, while a strong IgG response to all immunogens was detected with ELISA after two vaccinations. The higher number of immunogens contributed to a more robust total IgG response and correlating neutralizing activity against VACV, indicating the additive potential of each immunogen in generating immune response and nullifying VACV infection. Further, the mRNA vaccines elicited an antigen-specific CD4+ T cell response that is biased towards Th1. The mRNA vaccines with different combinations of EV and MV surface antigens protected a mouse model from a lethal dose VACV challenge, with the EV and MV antigens-combined vaccine offering the strongest protection. These findings provide insight into the protective mechanism of multi-valent mRNA vaccines against MPV, and also the foundation for further development of effective and safe mRNA vaccines for enhanced protection against monkeypox virus outbreak. [ABSTRACT FROM AUTHOR]

Background: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). Methods: Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results: From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3–93.2%). The median DoR was 19.3 (95% CI: 15.8–25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8–24.8) months and 22.0 (95% CI: 16.8–26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. Conclusions: Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. Trial registration: ClinicalTrials.gov, NCT03386955. [ABSTRACT FROM AUTHOR]

Purpose: Effective interventions to improve prognosis in non–small-cell lung cancer (NSCLC) are urgently needed. We assessed the effect of the early integration of interdisciplinary palliative care (based on WARM model) for patients with NSCLC on the quality of life (QoL), psychological state, cancer pain and nutritional status. Methods: In this randomized controlled trial, 120 newly diagnosed NSCLC patients were enrolled and randomly assigned (1:1) to the combined early palliative care (CEPC) group integrated with standard oncologic care or standard oncological care (SC) group. QoL and psychological state were assessed at baseline and at 24 weeks by Functional Assessment of Cancer Therapy-Lung (FACT-L) scale, the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-9 (PHQ-9), respectively. Cancer nutritional and pain status were assessed with the use of the Patient-Generated Subjective Global Assessment (PG-SGA) and Numerical Rating Scale (NRS), respectively. The primary outcome was the change in the quality of life, psychological state and nutritional status at 24 weeks. Analysis was by intention to treat. Results: 120 patients were enrolled: 60 in CEPC group (38 completed) and 60 in the SC group (32 completed). CEPC group had a better QoL than SC group (P <.05). In addition, fewer patients in the CEPC group than in the SC group had depressive (P =.005) symptoms. Furthermore, patients in CEPC group had a better nutritional status than SC group (P =.001). Conclusion: Among patients with non–small-cell lung cancer, early palliative care led to significant improvements in quality of life, psychological state and nutritional status. [ABSTRACT FROM AUTHOR]

Objective: Inflammation and malnutrition are common in patients with advanced lung cancer undergoing palliative care, and their survival time is limited. In this study, we created a prognostic model using the Inflam-Nutri score to predict the survival of these patients. Methods: A retrospective cohort study was conducted on 223 patients with advanced, histologically confirmed unresectable lung cancer treated between January 2017 and December 2018. The cutoff values of the neutrophil-albumin ratio (NAR) and Patient-Generated Subjective Global Assessment (PG-SGA) score were determined by the X-tile program. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analysis were performed to identify prognostic factors of overall survival (OS). We then established a nomogram model. The model was assessed by a validation cohort of 72 patients treated between January 2019 and December 2019. The predictive accuracy and discriminative ability were assessed by the concordance index (C-index), a plot of the calibration curve and risk group stratification. The clinical usefulness of the nomogram was measured by decision curve analysis (DCA). Results: The nomogram incorporated stage, supportive care treatment, the NAR and the PG-SGA score. The calibration curve presented good performance in the validation cohorts. The model showed discriminability with a C-index of 0.76 in the training cohort and 0.77 in the validation cohort. DCA demonstrated that the nomogram provided a higher net benefit across a wide, reasonable range of threshold probabilities for predicting OS. The survival curves of different risk groups were clearly separated. Conclusions: The NAR and PG-SGA scores were independently related to survival. Our prognostic model based on the Inflam-Nutri score could provide prognostic information for advanced palliative lung cancer patients and physicians. [ABSTRACT FROM AUTHOR]

In this work, two electronic nose (E-nose) prototypes for lung cancer detection via breath analysis are built. The instrumental variation between them is a critical problem, as it impacts on the generalization performance of classification model. The conventional domain adaption (DA) methods are based on the assumption that the data quality of both devices is high enough. However, it is not true in our case because the concentrations of volatile organic compounds (VOCs) biomarkers in breath are very low and the acquisition process of breath samples is prone to many confounding factors. As a countermeasure, a novel and effective two-step sparse unidirectional domain adaptation (SUDA) algorithm is proposed. In the first step, the data quality of each domain is improved, at the meantime, the distribution discrepancy between source and target domain is reduced by finding the common discriminative features via the sparse group lasso algorithm. In the second step, the distribution gap is further narrowed down by adopting the strategies of distribution alignment, local geometric characteristics preserving and label dependence constraint. Experimental results show that the proposed method is not only significantly effective for correcting instrumental variation in the two homemade lung-cancer-detection E-noses, but also demonstrates superior performance on a public E-nose instrumental variation dataset. [ABSTRACT FROM AUTHOR]

The bismuth tungstate with different morphologies was controllably synthesized by simple hydrothermal synthesis under different pH and different hydrothermal reaction time (HRT). Under the influence of these two conditions, the results show that with the increase of pH, the sample gradually changed from orthogonal phase Bi2WO6 to cubic Bi3.84W0.16O6.24 and the morphology changed from lamellas composed of nanorods to octahedral particles, as well as the photo-catalytic activity of Bi3.84W0.16O6.24 was far less than that of Bi2WO6. Additionally, with the increase of HRT, the thickness of flaky Bi2WO6 is thinner, the crystallinity is more stable, and the direction of growth is changed from lamellar to flower buds. The photo-catalytic activity of lamellar BWO-8/BWO-T-10 (prepared in lower pH and lower HRT) is the best. After radiation of 2 h, the degradation efficiency of tetracycline is 85% and the kinetic reaction rate constant is 0.0135 min−1. After three cycles of reusing, it still maintains high stability. The catalytic mechanism analysis shows that the active particle.OH produced by the photoelectron hole to the reaction has strong oxidizing property, which can quickly decompose tetracycline. [ABSTRACT FROM AUTHOR]

Rivers are a vital component of both urban and rural aquatic ecosystems, and the rapidly increasing pollution in rivers severely threatens the security of these ecosystems. In this study, the surface water quality in the Maozhou River basin, Guangdong Province, China, was assessed from 2018 to 2020 using multivariate statistical techniques and the Integrated Water Quality Index (IWQI). In addition, spatial trends in surface water quality were studied using a geographic information system. The results indicated that the water quality in 82.17% of the studied section met the Class V standard for surface water quality, with IWQI values ranging from 12.157 to 3.650. The surface water quality was clustered into eight groups and further divided into unsuitable (low quality) and suitable (acceptable quality) according to standard surface water quality thresholds (China in Environmental quality standards for surface water, 2002). Four groups (G1, G2, G3, and G4) were classified as unsuitable, because they fell short of the Class V standard for surface water quality. In these groups, industrial sewage, endogenous pollution, domestic sewage, and rainfall runoff, were the primary sources of pollution, and the main background pollutants for the water quality target of the functional zones were COD, NH3-N, TP, and LAS. The other four groups were classified as suitable. In these groups, endogenous pollution and rainfall runoff were the primary sources of pollution, and the main background pollutants for the water quality target of the functional zones were NH3-N and TP. Among them, NH3-N and LAS were recognized as responsive and sensitive to the surface water quality and spatio-temporal variability. Owing to pollution treatment and management measures undertaken by the Chinese government, the black-odorous water in the Maozhou River basin has disappeared, and the water quality in the Maozhou River basin has been maintained at the "medium and good" level. However, the surface water quality in the estuary region and the southwest tributary in the basin requires further improvement. This calls for further efforts to improve surface water quality and to properly deal with various sources of pollution in the watershed. This combined method has proved to be effective for surface water quality evaluation and management at river or basin scales. The results of this work are expected to provide a scientific foundation for aquatic ecosystem management and planning. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC) is a frequently diagnosed aggressive cancer all over the world. Small nucleolar RNAs (snoRNAs) are a group of non-coding mediatory RNAs. A previous report indicated that small nucleolar RNA 47 (SNORA47) is upregulated in NSCLC. However, the role of SNORA47 in NSCLC is unclear. Material and Methods: Cell proliferation was measured by immunofluorescence staining. Cell apoptosis and cycle of NSCLC were tested by flow cytometry and the protein expressions were investigated by Western-blot. Meanwhile, cell migration and invasion were detected by transwell assay. Xenograft mice model was established to detect the effect of SNORA47 knockdown on tumor growth of NSLC in vivo. Results: Knockdown of SNORA47 significantly inhibited the proliferation of NSCLC cells via inducing cell apoptosis. Moreover, migration and invasion of NSCLC cells were notably decreased by SNORA47 shRNA. SNORA47 knockdown significantly induced G1 arrest in NSCLC cells via regulation of p27 Kip1, CDK2, and cyclin D1. Meanwhile, SNORA47 shRNA inhibited EMT process and PI3K/Akt signaling in NSCLC cells. Finally, silencing of SNORA47 significantly inhibited the tumor growth of NSCLC in vivo. Conclusion: Knockdown of SNORA47 significantly inhibited the tumorigenesis of NSCLC via inhibition of PI3K/Akt signaling and EMT process. Thereby, our finding might shed a new light on exploring the strategies for the treatment of NSCLC. [ABSTRACT FROM AUTHOR]

Objective. Primary headache and obesity are highly prevalent disorders in the general population. Although many studies have reported an association between the two, there is still no overall comprehension about this relationship. To gain a more accurate understanding in this regard, we analyzed data from a 2011 cross-sectional study in Chongqing, China. Methods. Patients with a chief complaint of headache were administered a headache questionnaire and diagnosed by neurology doctors in accordance with the International Classification of Headache Disorders 2nd Edition (ICHD-II) criteria. Patients aged < 18 years or diagnosed with secondary headache were excluded. Results. Of 1327 patients who cited headache as the chief complaint, 16 were excluded for missing data, while 396 were diagnosed with chronic headache (177 chronic migraine [CM], 186 chronic tension-type headache [CTTH], and 33 other chronic headache) and 915 with episodic headache (369 episodic migraine [EM], 319 episodic tension-type headache [ETTH], and 227 other episodic headache). Chronic headache patients had a higher number of headache days per month, longer duration of headache history, and greater tendency to overuse analgesics than episodic headache patients. The CM and ETTH patients were more apt to be overweight and had a significantly greater body mass index (BMI; p < 0.05) than the EM and CTTH patients. Overweight (odds ratio [OR] = 3.64; 95% confidence interval (CI), 1.19–8.81) and obesity (OR = 28.63; 95% CI, 2.96–276.6) were independently associated with CM but not with other headaches, and this association was not influenced by other factors such as medication overuse. Conclusions. The relationship between headache and overweight/obesity varies depending on the type of primary headache. CM patients are more likely to have a higher body mass index than EM patients, while ETTH patients are more likely to be overweight/obese than CTTH patients. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains one of the leading causes of cancer-associated mortality. The overexpression of inhibitor of apoptosis-stimulating protein of p53 (iASPP) has been detected in GC tissues but the function of iASPP in the viability of GC cells and its underlying molecular mechanism remains unknown. Kruppel-like factor 4 (KLF4) is a tumor suppressor gene in GC and it may interact with p53. iASPP is an evolutionarily conserved inhibitor of p53, whereas KLF4 may be negatively associated with iASPP in GC. However, whether KLF4 has regulatory effects on iASPP remains to be investigated. The objective of the present study was to examine the function of iASPP and KLF4 in the proliferation of GC cells and to determine whether KLF4 has regulatory effects on iASPP. It was demonstrated that iASPP was upregulated and KLF4 was downregulated in GC cell lines. Downregulation of iASPP inhibited the proliferation and colony formation ability, and promoted the apoptosis of GC cells. Additionally, upregulation of KLF4 inhibited the proliferation and colony formation ability, and promoted apoptosis of GC cells. Furthermore, upregulation of KLF4 inhibited the expression of iASPP. Upregulation of iASPP following overexpression of KLF4 reversed the KLF4-mediated effects in GC cells. In vivo upregulation of KLF4 or downregulation of iASPP inhibited the growth of tumors, whereas upregulation of iASPP promoted the growth of tumors. In conclusion, iASPP may act as an oncogene that promotes the proliferation of GC cells. The results demonstrated that KLF4 was a negative regulatory factor of iASPP and that overexpression of iASPP inhibited the effects of KLF4. Thus, downregulation of KLF4 in GC may lead to overexpression of iASPP and promote the development of cancer. [ABSTRACT FROM AUTHOR]

The development of genetically engineered animals has brought with it increasing concerns about biosafety issues. We therefore evaluated the risks of growth hormone from transgenic goats, including the probability of horizontal gene transfer and the impact on the microbial community of the goats’ gastrointestinal tracts, feces and the surrounding soil. The results showed that neither the GH nor the neoR gene could be detected in the samples. Moreover, there was no significant change in the microbial community of the gastrointestinal tracts, feces and soil, as tested with PCR-denaturing gradient gel electrophoresis and 16S rDNA sequencing. Finally, phylogenetic analysis showed that the intestinal content, feces and soil samples all contained the same dominant group of bacteria. These results demonstrated that expression of goat growth hormone in the mammary of GH transgenic goat does not influence the microflora of the intestine, feces and surrounding soil. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to observe the therapeutic effect of cytokine induced killer (CIK) cells in combination with dendritic cells (DCs) on advanced solid carcinoma patients. Methods: Isolated peripheral blood mononuclear cells (PBMCs) from 110 advanced solid tumor patients. Added granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) to adherent cells to induce DCs, and sensitized DCs with antigens of autologous tumor cells or extrinsic tumor cell lines. Cultured suspending cells with interferon-γ (IFN-γ), interleukin-2 (IL-2) and CD3 monoclonal antibody (CD3 McAb) to prepare CIK cells, then co-cultured with DCs. After analyzing the phenotype and checking tumor markers and immune function, the autologous CIK cells and DCs were transfused into the cancer patients. Results: Forty-two patients with measurable nidus, 2 achieved complete remission (CR), 9 partial remission (PR) and 15 stable disease (SD), while 37 patients with immeasurable nidus, 25 had efficient response. The tumor markers and immune function both improved significantly compared with those before treatment. Conclusion: DCs and CIK cells combinational treatment is safe and effective on advanced solid carcinoma and provide a new and efficacious immunity therapeutic methods for the cancer patients. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced osteoporosis (GIOP) is a major cause of secondary osteoporosis, and the pathogenic mechanisms of GIOP remain to be elucidated. Here, we show a rapid dexamethasone-induced osteoporosis animal model using zebrafish scales. Intraperitoneal injection of dexamethasone over a 5-day period suppressed the regeneration of scales. Furthermore, the circularity of the newly formed regenerated scales was also slightly reduced compared to that of the control group on day 5. The changes in bone-related enzymes, such as cathepsin K, tartrate-resistant acid phosphatase (TRAP) for bone resorption, and alkaline phosphatase (ALP) for bone formation, provide insight into the progression of bone diseases; therefore, we further developed a method to measure the activities of cathepsin K, TRAP, and ALP using zebrafish scales. We found that a lysis buffer with detergent at neutral pH under sonication efficiently helped extract these three enzymes with high activity levels. Interestingly, treatment with a dexamethasone injection produced considerably higher levels of cathepsin K activity and a lower Ca/P ratio than those in the control group, suggesting that dexamethasone increased osteoclast activity, with no significant changes in the activities of TRAP and ALP. Our GIOP model and enzyme assay method could help to design better treatments for GIOP. [ABSTRACT FROM AUTHOR]

Chitosanase plays an important role in the production of chitooligosaccharides (CHOS), which possess various biological activities. Herein, a glycoside hydrolase (GH) family 46 chitosanase-encoding gene, csnB, was cloned from marine bacterium Bacillus sp. BY01 and heterologously expressed in Escherichia coli. The recombinant chitosanase, CsnB, was optimally active at 35 °C and pH 5.0. It was also revealed to be a cold-adapted enzyme, maintaining 39.5% and 40.4% of its maximum activity at 0 and 10 °C, respectively. Meanwhile, CsnB showed wide pH-stability within the range of pH 3.0 to 7.0. Then, an improved reaction condition was built to enhance its thermostability with a final glycerol volume concentration of 20%. Moreover, CsnB was determined to be an endo-type chitosanase, yielding chitosan disaccharides and trisaccharides as the main products. Overall, CsnB provides a new choice for enzymatic CHOS production. [ABSTRACT FROM AUTHOR]