A novel immune-related long noncoding RNA (lncRNA) pair model to predict the prognosis of triple-negative breast cancer.

Background: Breast cancer (BC) is the most prevalent cancer type and is the principal cause of cancer-related death in women. Anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) immunotherapy has shown promising effects in metastatic triple-negative breast cancer (TNBC), but the potential factors affecting its efficacy have not been elucidated. Immune-related long noncoding RNAs (irlncRNAs) have been reported to be involved in immune escape to influence the carcinogenic process through the PD-1/PD-L1 signaling pathway. Therefore, exploring the potential regulatory mechanism of irlncRNAs in PD-1/PD-L1 immunotherapy in TNBC is of great importance. Methods: We retrieved transcriptome profiling data from The Cancer Genome Atlas (TCGA) and identified differentially expressed irlncRNA (DEirlncRNA) pairs. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to construct a risk assessment model. Results: Receiver operating characteristic (ROC) curve analysis indicated that the risk model may serve as a potential prediction tool in TNBC patients. Clinical stage and risk score were proved to be independent prognostic predictors by univariate and multivariate Cox regression analyses. Subsequently, we investigated the correlation between the risk model and tumor-infiltrating immune cells and immune checkpoints. Finally, we identified USP30-AS1 through the StarBase and Multi Experiment Matrix (MEM) databases, predicted the potential target genes of USP30-AS1, and then discovered that these target genes were closely associated with immune responses. Conclusions: Our study constructed a risk assessment model by irlncRNA pairs regardless of expression levels, which contributed to predicting the efficacy of immunotherapy in TNBC. Furthermore, the lncRNA USP30-AS1 in the model was positively correlated with the expression of PD-L1 and provided a potential therapeutic target for TNBC.

Prognostic effect of masked morning hypertension in Chinese inpatients with non-dialysis chronic kidney disease: A multi-center retrospective study.

OBJECTIVE: This study aimed to elucidate the prognostic role of Masked Morning Hypertension (MMH) in non-dialysis-dependent chronic kidney disease (NDD-CKD). METHODS: 2,130 NDD-CKD patients of inpatient department were categorized into four blood pressure groups: clinical normotension (CH-), clinical hypertension (CH+) with morning hypertension (MH+), and without MH+ (MH-) respectively. The correlation between these four blood pressure types and the primary (all-cause mortality) and secondary endpoints (cardio-cerebrovascular disease [CVD] and end-stage kidney disease [ESKD]) was analyzed. RESULTS: The prevalences of morning hypertension and masked morning hypertension were 47.4% and 14.98%, respectively. Morning hypertension independently increased the risk of all-cause mortality (P=0.004) and CVD (P<0.001) but not ESKD (P=0.092). Masked morning hypertension was associated with heightened all-cause mortality (HR = 4.22, 95% CI = 1.31-13.59; P=0.02) and CVD events (HR = 5.14, 95% CI = 1.37-19.23; P=0.02), with no significant association with ESKD (HR = 1.18, 95% CI = 0.65-2.15; P=0.60). When considering non-CVD deaths as a competing risk factor, a high cumulative incidence of CVD events was observed in the masked morning hypertension group (HR = 5.16, 95% CI = 1.39-19.08). CONCLUSIONS: MMH is an independent risk factor for all-cause mortality and combined cardiovascular and cerebrovascular events in NDD-CKD patients, underscoring its prognostic significance. This highlights the need for comprehensive management of morning hypertension in this population.

Efficient tunable white emission and multiple reversible photoluminescence switching in organic Tin(IV) chlorides via regulating the host lattice environment of antimony ions for multifunctional applications.

The host lattice environments of Sb3+ has a great influence on its photophysical properties. Here, we synthesized three zero-dimensional organic metal halides of (TPA)2SbCl5 (1), Sb3+-doped (TPA)SnCl5(H2O)·2H2O (Sb3+-2), and Sb3+-doped (TPA)2SnCl6 (Sb3+-3). Compared with the intense orange emission of 1, Sb3+-3 has smaller lattice distortion, thus effectively suppressing the exciton transformation from singlet to triplet self-trapped exciton (STE) states, which makes Sb3+-3 has stronger singlet STE emission and further bring a white emission with a photoluminescence quantum efficiency (PLQE) of 93.4%. Conversely, the non-emission can be observed in Sb3+-2 even though it has a similar [SbCl5]2- structure to 1, which should be due to its indirect bandgap characteristics and the effective non-radiative relaxation caused by H2O in the lattice. Interestingly, the non-emission of Sb3+-2 can convert into the bright emission of Sb3+-3 under TPACl DMF solution treatment. Meanwhile, the white emission under 315 nm excitation of Sb3+-3 can change into orange emission upon 365 nm irradiation, and the luminescence can be further quenched by the treatment of HCl. Therefore, a triple-mode reversible luminescence switch of off-onI-onII-off can be achieved. Finally, we demonstrated the applications of Sb3+-doped compounds in single-component white light illumination, latent fingerprint detection, fluorescent anti-counterfeiting, and information encryption.

Eco-friendly preparation and characterization of high-performance electrothermal graphene-AgNPs/lignocellulose composites.

Graphene-based (Gr-based) electrothermal heaters, due to their light weight, low electrical resistance, high thermal conductivity, and easy accessibility, have attracted widespread attention in the field of electrothermal heating. To achieve a high steady-state temperature in electrothermal heaters under low voltage, here we constructed a Gr-based film with low electrical resistance. Firstly, we employed non-toxic vitamin C to reduce silver nitrate for the in situ chemical deposition of silver nanoparticles (AgNPs) on the Gr surface. The SEM results confirmed that the AgNPs were uniformly deposited on the Gr surface. The synergistic interaction between AgNPs and Gr provided high-speed electrons transport paths for the film. On the other hand, we employed biodegradable lignocellulose fiber (LCF) as a dispersant and film-forming agent. The aromatic ring structure of LCF interacts with Gr via π-π interactions, aiding the dispersion of Gr in aqueous solutions. SEM results revealed that LCF permeated through the surfaces and interstices of the two-dimensional Gr sheets, providing mechanical support for the composite film. This approach enables the creation of freestanding Gr-AgNPs/LCF electrothermal composites. The resistivity and electrothermal results demonstrated that the obtained 20 wt% Gr-based composite film possessed low electrical resistance (5.4 Ω sq-1) and exhibited an outstanding saturated temperature of 214 °C under a very low input voltage of 7 V. The preparation method of this Gr-based composite film is simple, easy to operate, and environmentally friendly, providing a new reference for the preparation of eco-friendly and high-performance resistance heating electronics.

Association between genetically proxied PCSK9 inhibition and systemic lupus erythematosus risk: A mendelian randomization study.

BACKGROUND: Preclinical and epidemiological studies suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) had a potential effect on the development of SLE, but it was unclear whether a causal relationship exists. We aimed to investigate the association between genetically proxied inhibition of PCSK9 and the risk of SLE using a two-sample Mendelian randomization (MR) approach. METHODS: Single nucleotide polymorphisms (SNPs) associated with PCSK9 were extracted from pooled data obtained from the Global Lipid Genetics Consortium (GLGC) Genome-wide Association Study (GWAS) related to LDL-c levels, which was used as a proxy for PCSK9 inhibition. Pooled statistics for SLE were obtained from an independent GWAS dataset including 5201 SLE patients and 9066 controls. Inverse variance-weighted random-effects models were used to examine the association between genetically proxied inhibition of PCSK9 and the risk of SLE. MR-Egger, weighted median, weighted mode, Simple mode, and co-location analyses were used as sensitivity analyses to test the robustness of the analyses. RESULTS: Genetically proxied inhibition of PCSK9 was associated with a reduced risk of SLE (OR = 0.51, 95% CI = 0.34 to 0.77, p = .001). This finding was replicated in an earlier GLGC GWAS analysis (OR = 0.59, 95% CI = 0.40 to 0.87, p = .007). Sensitivity analysis ensured that the results were robust. Co-localization analysis did not find evidence of shared causal variation between PCSK9 and SLE. CONCLUSIONS: This Mendelian randomization study showed that PCSK9 was associated with SLE pathogenesis, and its inhibition was associated with a reduced risk of SLE. This study has offered a prospective therapeutic avenue for intervening in the progression of SLE by inhibiting PCSK9 levels.

Underestimation of SARS-CoV-2 in wastewater due to single or double mutations in the N1 qPCR probe binding region.

Wastewater surveillance using RT-qPCR has now been widely adopted to track circulating levels of SARS-CoV-2 virus in many sewersheds. The CDC qPCR assays targeting two regions (N1 and N2) within the N gene are commonly used, but a discrepancy between the two biomarkers has been noticed by independent studies using these methods since late 2021. The reason is presumed to be due to mutations in regions targeted by the N1 qPCR probe. In this study, we systematically investigated and unequivocally confirmed that the underlying reason for this discrepancy was mutations in the N1 probe target, and that a single mutation could cause a significant drop in signal. We first confirmed the proportion of related mutations in wastewater samples (Jan 2021-Dec 2022) using nested PCR and LC-MS. Based on relative proportions of N1 alleles, we separated the wastewater data into four time periods corresponding to different variant waves: Period I (Alpha and Delta waves with 0 mutation), Period II (BA.1/BA.2 waves with a single mutation found in all Omicron strains), Period III (BA.5.2* wave with two mutations), and Period IV (BQ.1* wave with two mutations). Significantly lower N1 copies relative to N2 copies in samples from Periods II-IV compared to those from Period I was observed in wastewater. To further pinpoint the extent to which each mutation impacted N1 quantification, we compared the qPCR response among different synthetic oligomers with corresponding mutations. This study highlighted the impact of even just one or two mutations on qPCR-based wastewater surveillance of SARS-CoV-2.

Designing transition metal-based porous architectures for supercapacitor electrodes: a review.

Over the past decade, transition metal (TM)-based electrodes have shown intriguing physicochemical properties and widespread applications, especially in the field of supercapacitor energy storage owing to their diverse configurations, composition, porosity, and redox reactions. As one of the most intriguing research interests, the design of porous architectures in TM-based electrode materials has been demonstrated to facilitate ion/electron transport, modulate their electronic structure, diminish strain relaxation, and realize synergistic effects of multi-metals. Herein, the recent advances in porous TM-based electrodes are summarized, focusing on their typical synthesis strategies, including template-mediated assembly, thermal decomposition strategy, chemical deposition strategy, and host-guest hybridization strategy. Simultaneously, the corresponding conversion mechanism of each synthesis strategy are reviewed, and the merits and demerits of each strategy in building porous architectures are also discussed. Subsequently, TM-based electrode materials are categorized into TM oxides, TM hydroxides, TM sulfides, TM phosphides, TM carbides, and other TM species with a detailed review of their crystalline phase, electronic structure, and microstructure evolution to tune their electrochemical energy storage capacity. Finally, the challenges and prospects of porous TM-based electrode materials are presented to guide the future development in this field.

Identification and Biological Evaluation of a Novel Small-Molecule Inhibitor of Ricin Toxin.

The plant-derived toxin ricin is classified as a type 2 ribosome-inactivating protein (RIP) and currently lacks effective clinical antidotes. The toxicity of ricin is mainly due to its ricin toxin A chain (RTA), which has become an important target for drug development. Previous studies have identified two essential binding pockets in the active site of RTA, but most existing inhibitors only target one of these pockets. In this study, we used computer-aided virtual screening to identify a compound called RSMI-29, which potentially interacts with both active pockets of RTA. We found that RSMI-29 can directly bind to RTA and effectively attenuate protein synthesis inhibition and rRNA depurination induced by RTA or ricin, thereby inhibiting their cytotoxic effects on cells in vitro. Moreover, RSMI-29 significantly reduced ricin-mediated damage to the liver, spleen, intestine, and lungs in mice, demonstrating its detoxification effect against ricin in vivo. RSMI-29 also exhibited excellent drug-like properties, featuring a typical structural moiety of known sulfonamides and barbiturates. These findings suggest that RSMI-29 is a novel small-molecule inhibitor that specifically targets ricin toxin A chain, providing a potential therapeutic option for ricin intoxication.

Deep learning based model predictive controller on a magnetic levitation ball system.

The magnetic levitation (maglev) ball system is a prototypical Single-Input-Single-Output (SISO) system, characterized by its pronounced nonlinearity, rapid response, and open-loop instability. It serves as the basis for many industrial devices. For describing the dynamics of the maglev ball system precisely in the pseudo linear model, the long short-term memory (LSTM) based auto-regressive model with exogenous input variables (LSTM-ARX) is proposed. Firstly, the LSTM network is modified by incorporating the auto-regressive structure with respect to sequence input, allowing it to deduce a locally linearized model without the need for Taylor expansion. Then, the LSTM-ARX model is transformed into a linear parameter varying (LPV) state space model, and upon this foundation, a model predictive controller (MPC) is proposed. Specifically, when deducing the MPC, the deep learning-based model is linearized by fixing its state input at the current state, so that the nonlinear, non-convex optimization problem can be converted to a finite-horizon quadratic programming problem, thereby deriving the explicit form of MPC. To further enhance the efficiency of the controller in real-time control tasks, a predictive functional controller (PFC) is proposed. It employs multiple nonlinear functions to fit the control sequence, thereby reducing the number of decision variables of the on-line optimization problem in MPC. The proposed controller was successfully applied to the real-time control of the maglev ball system. Simulation and real-time control experiments have validated the improvement in transient performance and efficiency of the LSTM-ARX model-based PFC (LSTM-ARX-PFC).

Effects of Aerobic Exercise Combined With Attentional Bias Modification in the Care of Male Patients With a Methamphetamine Use Disorder.

OBJECTIVE: It remains unclear which individual or combined strategies are most beneficial for methamphetamine use disorders (MUDs). We compared the effects of aerobic exercise, attentional bias modification, and combined intervention on male patients with MUD. METHOD: One hundred male patients with MUD were randomly assigned to combined intervention, aerobic exercise, attentional bias modification, or control groups (25 patients per group). The 8-week intervention protocol included three 60-minute sessions of aerobic exercises per week. Primary outcomes included high- and low-frequency heart rate variability, executive function, and cardiorespiratory fitness measured by customized software, computerized tests, and the Harvard step test, respectively. Secondary outcomes included psychiatric symptoms, drug craving, training acceptability, and persistence. RESULTS: Participant characteristics were matched between groups at baseline. Executive function, heart rate variability, cardiorespiratory fitness, drug craving, and most psychiatric symptoms had significant time-group interactions at posttest (p < .05, η2 = .08-.28). Compared with the attentional bias modification and control groups, the combined intervention and aerobic exercise groups improved significantly in executive function, heart rate variability, cardiorespiratory fitness, and most secondary outcomes. In addition, high-frequency heart rate variability and cardiorespiratory fitness in the aerobic exercise group were significantly higher than those in the combined intervention group. CONCLUSIONS: Combination strategies showed comparable efficacy to aerobic exercise alone in improving executive function, psychiatric symptoms, and drug craving and significantly exceeded other conditions. For heart rate variability and cardiorespiratory fitness, aerobic exercise alone was the most effective. For acceptability and persistence, combination strategies were preferred over single-domain training and health education intervention.

Structural insights into curdlan degradation via a glycoside hydrolase containing a disruptive carbohydrate-binding module.

BACKGROUND: Degradation via enzymatic processes for the production of valuable ß-1,3-glucooligosaccharides (GOS) from curdlan has attracted considerable interest. CBM6E functions as a curdlan-specific ß-1,3-endoglucanase, composed of a glycoside hydrolase family 128 (GH128) module and a carbohydrate-binding module (CBM) derived from family CBM6. RESULTS: Crystallographic analyses were conducted to comprehend the substrate specificity mechanism of CBM6E. This unveiled structures of both apo CBM6E and its GOS-complexed form. The GH128 and CBM6 modules constitute a cohesive unit, binding nine glucoside moieties within the catalytic groove in a singular helical conformation. By extending the substrate-binding groove, we engineered CBM6E variants with heightened hydrolytic activities, generating diverse GOS profiles from curdlan. Molecular docking, followed by mutation validation, unveiled the cooperative recognition of triple-helical ß-1,3-glucan by the GH128 and CBM6 modules, along with the identification of a novel sugar-binding residue situated within the CBM6 module. Interestingly, supplementing the CBM6 module into curdlan gel disrupted the gel's network structure, enhancing the hydrolysis of curdlan by specific ß-1,3-glucanases. CONCLUSIONS: This study offers new insights into the recognition mechanism of glycoside hydrolases toward triple-helical ß-1,3-glucans, presenting an effective method to enhance endoglucanase activity and manipulate its product profile. Furthermore, it discovered a CBM module capable of disrupting the quaternary structures of curdlan, thereby boosting the hydrolytic activity of curdlan gel when co-incubated with ß-1,3-glucanases. These findings hold relevance for developing future enzyme and CBM cocktails useful in GOS production from curdlan degradation.

High throughput screening of pure silica zeolites for CF4 capture from electronics industry gas.

The capture and separation of CF4 from CF4/N2 mixture gas is a crucial issue in the electronics industry, as CF4 is a commonly used etching gas and the ratio of CF4 to N2 directly affects process efficiency. Utilizing high-throughput computational screening techniques and grand canonical Monte Carlo (GCMC) simulations, we comprehensively screened and assessed 247 types of pure silicon zeolite materials to determine their adsorption and separation performance for CF4/N2 mixtures. Based on screening, the relationships between the structural parameters and adsorption and separation properties were meticulously investigated. Four indicators including adsorption selectivity, working capacity, adsorbent performance score (APS), and regenerability (R%) were used to evaluate the performance of adsorbents. Based on the evaluation, we selected the top three best-performing zeolite structures for vacuum swing adsorption (LEV, AWW and ESV) and pressure swing adsorption (AVL, ZON, and ERI) processes respectively. Also, we studied the preferable adsorption sites of CF4 and N2 in the selected zeolite structures through centroid density distributions at the molecule level. We expect the study may provide some valuable guidance for subsequent experimental investigations on adsorption and separation of CF4/N2.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

Correlation of the serum cell division cycle 42 with CD4+ T cell subsets and in-hospital mortality in Stanford type B aortic dissection patients.

Objective: Cell division cycle 42 (CDC42) regulates CD4+ T-cell differentiation and participates in vascular stiffness and atherosclerosis and is involved in the progression of Stanford type B aortic dissection (TBAD). This study aimed to explore the correlation between serum CDC42 level and CD4+ T cell subsets and in-hospital mortality in TBAD patients. Methods: Serum CDC42 and peripheral blood T-helper (Th) 1, Th2, and Th17 cells were detected in 127 TBAD patients by enzyme-linked immunosorbent assay and flow cytometry, respectively. Serum CDC42 was also quantified in 30 healthy controls. Results: Serum CDC42 was decreased in TBAD patients vs. healthy controls (median [interquartile range (IQR)]: 418.0 (228.0-761.0) pg/ml vs. 992.0 (716.3-1,445.8) pg/ml, P < 0.001). In TBAD patients, serum CDC42 was negatively correlated with Th17 cells (P = 0.001), but not Th1 (P = 0.130) or Th2 cells (P = 0.098). Seven (5.5%) patients experienced in-hospital mortality. Serum CDC42 was reduced in patients who experienced in-hospital mortality vs. those who did not (median (IQR): 191.0 (145.0-345.0) pg/ml vs. 451.5 (298.3-766.8) pg/ml, P = 0.006). By receiver operating characteristic analysis, serum CDC42 showed a good ability for estimating in-hospital mortality [area under curve = 0.809, 95% confidence interval (CI) = 0.662-0.956]. By the multivariate logistic regression analysis, elevated serum CDC42 [odd ratio (OR) = 0.994, 95% CI = 0.998-1.000, P = 0.043] was independently correlated with lower risk of in-hospital mortality, while higher age (OR = 1.157, 95% CI = 1.017-1.316, P = 0.027) was an independent factor for increased risk of in-hospital mortality. Conclusion: Serum CDC42 negatively associates with Th17 cells and is independently correlated with decreased in-hospital mortality risk in TBAD patients.

Effect of Liver Segments and Hepatic Fibrosis Grade on Repeatability, Reliability, and Diagnostic Efficiency of Intravoxel Incoherent Motion.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is considered a potential marker of hepatic fibrosis (HF). OBJECTIVE: To explore the influencing factors of repeatability and reliability in IVIM-DWI parameters of ROI-based liver segments in participants with HF and healthy volunteers (HV) and to assess the diagnostic efficiency of these parameters in HF. METHODS: Participants with early HF (EHF, n=59) or advanced HF (AHF, n=38) and HV (n=48) were recruited. Two examiners measured IVIM data using mono-, bi-exponential and stretched exponential models. The results and influencing factors of repeatability and reliability of IVIM-DWI, and the diagnostic efficiency were analyzed. RESULTS: The repeatability of D* (CV: 26.62-41.47%) and DDC (CV: 18.01-34.40%) was poor, the repeatability of ADC (CV: 4.95-9.76%), D (CV: 7.09-15.52%), f (CV: 9.35-17.15%), and α (CV: 7.48-13.81%) was better; ordered logistic regression showed statistically significant results of IVIM-derived parameters; the reliability showed no obvious trend, and ordered logistic regression showed statistically significant results of IVIMderived parameters, groups, and partial hepatic segments (all p<0.001). IVIM-derived parameters with relatively good repeatability (CV<20%) and reliability (ICC>0.4) were used to establish regression models for differential diagnosis. The AUC of regression models was 0.744-0.783 (EHF vs. AHF), but no statistically significant parameters were found in the HV vs EHF comparison. CONCLUSION: IVIM-derived parameters were the most important factors affecting the repeatability and reliability, while staging of HF and hepatic segments may be the influencing factors of reliability. IVIM-derived parameters showed medium diagnostic efficiency in distinguishing between EHF and AHF.