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The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients. [ABSTRACT FROM AUTHOR]

Social stability risk posed by energy infrastructure projects can seriously affect urban sustainable development. There is thus a need to better understand how risk strategies are designed. However, there is few considerations on risk strategy design by breaking causal relationships. This research innovatively explores social stability risk variables by content mining, develops causal relationships of the social stability risk variables via Fault Tree Analysis (FTA) method, explores core risk variables and critical causal relationships by social network analysis (SNA) method, designs and validates risk strategies. The findings show that: 1) From the overall risk network perspective, the risk network contain 8 core risk variables. 2) From individual risk network perspective, there are 75 critical causal relationships. The top 3 critical causal relationships contain: projects that destroy the cultural landscape would be regarded as threating national security, which often inspires demonstrations among the local people and the line betweenness is the largest (35.589). Traffic congestion by the project is the main reason to cause local small-scale public petition, and the line betweenness is 35.075. Projects that threaten the ecological environment often bring psychological rejection of the project by the local public, and the line betweenness is 30.837. 3) Two scenarios are evaluated in terms of basic scenario and the experiment group scenario. Compared with the basic scenario, risk strategies considering causal relationships have significant effectiveness. The overall risk network density has reduced by 35.22%. The clustering coefficients has decreased by 16.20%. Intermediate central potential has reduced by 9.49%. This study offers a good reference for project managers to complete the sustainable risk control. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is associated with kidney fibrosis. A previous study revealed that periostin (POSTN) contributes to kidney fibrosis. This study examined the role of POSTN in DN. The urinary concentrations of POSTN and TNC increased according to the severity of DN in human samples. Streptozotocin (STZ) was administered after unilateral nephrectomy (UNXSTZ) to induce DN in wild-type and Postn-null mice. Four experimental groups were generated: wild-typeham (WT Sham), wild-type UNXSTZ (WT STZ), Postn-null Sham (KO Sham), and Postn-null UNXSTZ (KO STZ). After 20 weeks, the KO STZ group had lower levels of urine albumin excretion, glomerular sclerosis, and interstitial fibrosis than those of the WT STZ group. Additionally, the KO STZ group had lower expression of fibrosis markers, including TNC. The KO STZ group showed better glucose regulation than the WT STZ model. Furthermore, the KO STZ group exhibited significantly preserved pancreatic islet integrity and insulin expression. HK-2 cells were used to observe the aggravation of fibrosis caused by POSTN under TGF-β conditions. We stimulated INS-1 cells with streptozotocin and evaluated the viability of these cells. The anti-POSTN antibody treatment of INS-1 cells with streptozotocin resulted in higher cell viability than that with treatment with streptozotocin alone. The absence of POSTN in DN contributes to renal fibrosis alleviation by improving pancreatic β-cell function. Additionally, there is an association between POSTN and TNC. [ABSTRACT FROM AUTHOR]

Objective: Total neoadjuvant therapy (TNT) combining chemoradiotherapy (CRT) with chemotherapy (CT) was a novel pre-surgical approach to cancer treatment. This meta-analysis aimed to compare the clinical outcomes between neoadjuvant CRT (nCRT) with induction CT and nCRT with consolidated CT in locally advanced rectal cancer (LARC) patients. Method: In July 2022, a literature search was conducted using the following public databases: PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science, retrieved all relevant articles comparing nCRT-combining induction CT with nCRT-combining-consolidated CT treatments for LARC patients. Results: Four eligible studies were identified, including a total of 995 LARC patients: 473 in the nCRT with consolidated CT group and 522 in the nCRT with induction CT group. The organ preservation (OP) rate of the nCRT with consolidated CT group was higher than that of the nCRT with induction CT group (RR [relative risk]: 1.53; 95% CI (confidence interval): 1.09–2.14). The pathological complete response (PCR, RR: 1.22; 95% CI 0.37–2.17), the 3-year disease-free survival (DFS, RR 1.02; 95% CI 0.71–1.46), the local recurrence (LR, RR 0.98; 95% CI 0.52–1.85), rates of R0 resection (RR 0.74; 95% CI 0.55–1.10), compliance (RR 0.52; 95% CI 0.12–2.26), and grade 3-–4 toxicities (RR 0.78; 95% CI 0.57–1.06) were all similar between the two groups. Conclusion: In this meta-analysis of TNT regimens for rectal cancer, consolidative CT following nCRT was associated with similar PCR, 3-year DFS, LR, R0 resection, compliance, and grade 3–4 toxicities compared to induction CT prior to nCRT but a higher rate of organ preservation. [ABSTRACT FROM AUTHOR]

Overcoming tumor-mediated immunosuppression and enhancing cytotoxic T-cell activity within the tumor microenvironment are two central goals of immuno-oncology (IO) drug discovery initiatives. However, exploratory assays involving immune components are often plagued by low-throughput and poor clinical relevance. Here we present an innovative ultra-high-content assay platform for interrogating T-cell-mediated killing of 3D multicellular tumor spheroids. Employing this assay platform in a chemical genomics screen of 1800 annotated compounds enabled identification of small molecule perturbagens capable of enhancing cytotoxic CD8+ T-cell activity in an antigen-dependent manner. Specifically, cyclin-dependent kinase (CDK) and bromodomain (BRD) protein inhibitors were shown to significantly augment anti-tumor T-cell function by increasing cytolytic granule and type II interferon secretion in T-cells in addition to upregulating major histocompatibility complex (MHC) expression and antigen presentation in tumor cells. The described biotechnology screening platform yields multi-parametric, clinically-relevant data and can be employed kinetically for the discovery of first-in-class IO therapeutic agents. Jeremy To et al. develop an ultra-high-content assay platform used to interrogate T-cell-mediated killing of 3D multicellular tumor spheroids. They screen 1,800 annotated compounds to identify small molecules that enhance cytotoxic CD8+ T-cell activity in an antigen-dependent manner, demonstrating the utility of this assay platform. [ABSTRACT FROM AUTHOR]

In this paper, a novel global optimization algorithm, named as Maxwell’s equations derived optimization (MEDO), is proposed. Using the Maxwell’s equations to analyse the behaviors of the time-varying current, the Ampere force is obtained from Fleming’s left hand rule. MEDO introduces an ‘Ampere force’ term, which is derived from Maxwell’s equations and is rigorous in physics, to drive the variables to the global optimal solution in the search space. In addition, introducing ‘gravity’ to MEDO can increase the stability of the optimizations. 11 classical benchmarks are tested, and results show that MEDO can always converge to numerical optimal solutions. To evaluate the proposed MEDO in solving the electromagnetic problems, four practical engineering applications are considered including the linear antenna array synthesis, frequency selected surface optimization, numerical dispersion reduction for finite-difference method, and parameters extraction of typical waveform. These examples are significant in electromagnetics, but tough to be solved because of their high dimensionality and strong nonlinearity. Numerical results show that MEDO can outperform several classic optimization methods, like wind driven optimization (WDO) and particle swarm optimization (PSO). Therefore, the electromagnetics-inspired MEDO is robust and of great potential in solving the electromagnetic optimization problems. [ABSTRACT FROM AUTHOR]

Predicting the risk of end-stage renal disease (ESRD) progression facilitates appropriate nephrology care of patients with chronic kidney disease (CKD). Previously, the kidney failure risk equations (KFREs) were developed and validated in several cohorts. The purpose of this study is to validate the KFREs in a Korean population and to recalibrate the equations. A total of 38,905 adult patients, including 13,244 patients with CKD stages G3–G5, who were referred to nephrology were recruited. Using the original KFREs (4-, 6- and 8-variable equations) and recalibration equations, we predicted the risk of 2- and 5-year ESRD progression. All analyses were conducted in CKD stages G3-G5 patients as well as the total population. In CKD stages G3–G5 patients, All the original 4-, 6- and 8-variable equations showed excellent areas under the receiver operating characteristic curve of 0.87 and 0.83 for the 2- and 5-year risk of ESRD, respectively. The results of net reclassification improvement, integrated discrimination index and Brier score showed that recalibration improved the prediction models in some cases. The original KFREs showed high discrimination in both CKD stages G3–G5 patients and the total population referred to nephrology in this large Korean cohort. KFREs can be implemented in Korean health systems and can guide nephrology referrals and other CKD-related treatment decisions. [ABSTRACT FROM AUTHOR]

In this paper, a single defect in graphene was created by an Au nanoparticle attached to atomic force tip working in tapping mode. Then it was investigated by tip-enhanced Raman spectroscopy (TERS). The TERS tip interacted with the graphene are able to induce an atomic deformation of carbonic structure which then can be recovered after retracting the tip. The reversible defect was confirmed by the iterative observation of D-band Raman signal of graphene as the tip force on and off. Further more, the Au particles as a nano-antenna can enhance the weak D-band signal from the single graphene defect significantly. These finds will give us better understanding of the origination of graphene defects and the interaction between nanoparticles and graphene. [ABSTRACT FROM AUTHOR]

Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form. [ABSTRACT FROM AUTHOR]