Recent Progress on Piezoelectric Materials and Pyroelectric Materials for Photoelectrochemical Water Splitting.

Directly transforming solar energy into chemical compounds via photocatalytic water splitting can continually producing hydrogen, which is regarded as one of the ultimate sustainable energy sources. The key point of achieving a high photoelectrochemical (PEC) water splitting performance is the successful design and synthesis of high-efficient photocatalysis. However, the slow separation and fast recombination of photo generated charge carriers greatly limits the utilization of solar energy resulting in low PEC water splitting efficiency. Recently, piezoelectric/pyroelectric effect assisted PEC water splitting brings new sight on improving charger separate and transfer behaviors. In this review, the recent advancements and state-of-the-art progress in piezoelectric/pyroelectric effect assisted PEC water splitting are summarized and discussed. Different types of photocatalysts are classified according to their chemical constitutions and the corresponding advantages are also reviewed. Furthermore, the coupling of piezoelectric effect and pyroelectric effect is also introduced. Finally, the prospects, critical challenges and promising strategies for the application of piezoelectric/pyroelectric materials in PEC water splitting are highlighted.

Recommended assessment and management of sleep disordered breathing in patients with atrial fibrillation, hypertension and heart failure: Taiwan Society of Cardiology/Taiwan Society of sleep Medicine/Taiwan Society of pulmonary and Critical Care Medicine joint consensus statement.

Sleep disordered breathing (SDB) is highly prevalent and may be linked to cardiovascular disease in a bidirectional manner. The Taiwan Society of Cardiology, Taiwan Society of Sleep Medicine and Taiwan Society of Pulmonary and Critical Care Medicine established a task force of experts to evaluate the evidence regarding the assessment and management of SDB in patients with atrial fibrillation (AF), hypertension and heart failure with reduced ejection fraction (HFrEF). The GRADE process was used to assess the evidence associated with 15 formulated questions. The task force developed recommendations and determined strength (Strong, Weak) and direction (For, Against) based on the quality of evidence, balance of benefits and harms, patient values and preferences, and resource use. The resulting 11 recommendations are intended to guide clinicians in determining which the specific patient-care strategy should be utilized by clinicians based on the needs of individual patients.

Construction of [NbO]6-x -xS Structure to Change Charge Density and Regulate Spontaneous Polarization to Achieve Efficient Pyro-Photo-Electric Water Splitting System of NaNbO3.

Pyroelectric materials in the field of photoelectrochemical (PEC) water splitting still face the problems of difficult low spontaneous polarization intensity and excessive carrier recombination. Based on the above problems, we altered the interaction between S-Nb-S in the [NbO]6-x -xS structure, and the constructed [NbO]6-x -xS structure achieved the regulation of charge density change and spontaneous polarization. The results show that under the stimulation of light and temperature fluctuations, the current density of the NS-4 photoanode is as high as 0.574 mA/cm2 at 1.23 VRHE , which is about 1.59 times higher than the pure NaNbO3 current density value, and the NS -4 photoanode achieves IPCE value of 16.08 %. The first-principles density-functional theory calculations (DFT) reveal the principle of the [NbO]6-x -xS structure for the suppression function of the carrier recombination and the improvement function of the pyroelectric effect. The analysis shows that the S-doping leads to the weakening of S-Nb-S interactions in the [NbO]6-x -xS structure, which improves the pyroelectric effect and suppresses the photo/pyro-generated carrier recombination, and effectively enhances the performance of the pyro-photo-electric synergistic water splitting system. This work promotes the development of pyroelectric materials in the field of photoelectrochemical water splitting.

Nickel/Copper Cooperative Catalysis Decarbonylative Heteroarylation of Aryl Anhydrides with Benzoxazoles via C-O/C-H Coupling.

A new strategy for the synthesis of 2-arylbenzoxazole derivatives via nickel-/copper-catalyzed decarbonylative heteroarylation of aryl anhydrides via C-O/C-H coupling has been developed. The reaction is promoted by a user-friendly, inexpensive, and air- and moisture-stable Ni precatalyst. A variety of 2-arylbenzoxazole derivatives have been successfully synthesized and have good functional group tolerance in this process, which afforded products in moderate-to-excellent yields.

P2 purinergic receptors regulate the progression of colorectal cancer.

More and more studies have revealed that P2 purinergic receptors play a key role in the progression of colorectal cancer (CRC). P2X and P2Y purinergic receptors can be used as promoters and regulators of CRC and play a dual role in the progression of CRC. CRC microenvironment is rich in ATP and its cleavage products (ADP, AMP, Ado), which act as activators of P2X and P2Y purinergic receptors. The activation of P2X and P2Y purinergic receptors regulates the progression of CRC mainly by regulating the function of immune cells and mediating different signal pathways. In this paper, we focus on the specific mechanisms and functional roles of P2X7, P2Y12, and P2Y2 receptors in the growth and progression of CRC. The antagonistic effects of these selective antagonists of P2X purinergic receptors on the growth, invasion, and metastasis of CRC were further discussed. Moreover, different studies have reported that P2X7 receptor can be used as an effective predictor of patients with CRC. All these indicate that P2 purinergic receptors are a key regulator of CRC. Therefore, antagonizing P2 purinergic receptors may be an innovative treatment for CRC.

ZFX-mediated upregulation of CEBPA-AS1 contributes to acute myeloid leukemia progression through miR-24-3p/CTBP2 axis.

Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML.

Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 µM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1ß and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.

Metastasis pattern and prognosis in children with neuroblastoma.

BACKGROUND: We aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis. METHOD: Data of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010-2018). Pearson's chi-square test, Kaplan-Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis. RESULTS: The overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III-IV (OR: 26.228, P < 0 .001) and 5-10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB. CONCLUSION: Metastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.

The impact of the overuse of short-acting ß2-agonists on the risk of sepsis and septic shock.

BACKGROUND: Overuse of short-acting ß-agonists (SABAs) could be associated with increased acute exacerbations and mortality in patients with asthma. However, the role of SABAs in sepsis has not been well studied. OBJECTIVES: We sought to investigate the association between the overuse of SABAs and sepsis in patients with asthma. METHODS: Between 2001 and 2013, patients with asthma were identified from Taiwan asthma pay-for-performance program database, but patients with prior sepsis were excluded. The overuse of SABAs was defined as the use of 3 or more canisters annually. RESULTS: A total of 28,033 patients were found to have overused SABAs (overuse group), and 155,453 patients had acceptable use of SABAs (control group). Using propensity score matching method with 1:1 ratio, we had 2 subgroups with similar baseline characteristic and each group had 20,542 patients. The incidence of sepsis during the follow-up period was 1.26 per 100 person-years in the SABA overuse group, which was higher than in the control group (0.94 per 100 person-years). The crude and adjusted hazard ratios were 1.35 (95% CI, 1.26-1.44) and 1.33 (95% CI, 1.24-1.43), respectively. The SABA overuse group also had a higher risk of sepsis within 1 year than the control group (adjusted odds ratio, 1.34; 95% CI, 1.09-1.64). The incidence of septic shock during the follow-up period was 0.44 per 100 person-years in the SABA overuse group, which was higher than in the control group (0.33 per 100 person-years). The crude and adjusted hazard ratios were 1.32 (95% CI, 1.17-1.48) and 1.28 (95% CI, 1.14-1.44), respectively. Subgroup analysis consistently revealed a higher incidence of sepsis in the SABA overuse group than in the control group in all age and male groups before and after propensity score matching. CONCLUSIONS: The overuse of SABA could be associated with an increased risk of sepsis and septic shock in the patient with asthma in Taiwan.

Inhaled Corticosteroids Increase Risk of Nontuberculous Mycobacterial Lung Disease: A Nested Case-Control Study and Meta-analysis.

Studies on use of inhaled corticosteroids (ICS) and the risk of nontuberculous mycobacterial lung disease (NTM-LD) are limited and have some conflicting results. We recruited 1235 NTM-LD patients and found that ICS use within 1 year was associated with increased NTM-LD, and the risk increased with elevated ICS dose and cumulative duration. Discontinuation of ICS use for more than 120 days could reduce the risk of NTM-LD to an insignificant level. For NTM species, the development of NTM-LD by ICS was highest for Mycobacterium kansasii lung disease. The pooled results of the meta-analysis showed that ICS use might increase the risk of NTM-LD with dose response in medium and high dose of daily ICS. In addition, budesonide had a smaller impact on the risk of NTM-LD than other ICS medications. The present study and meta-analysis provide evidence for ICS adjustment, including dose, discontinuation effect, and medications to possibly reduce the risk of NTM-LD.

Light-Assisted Li-O2 Batteries with Lowered Bias Voltages by Redox Mediators.

The enormous overpotential caused by sluggish kinetics of the oxygen reduction reaction and the oxygen evolution reaction prevents the practical application of Li-O2 batteries. The recently proposed light-assisted strategy is an effective way to improve round-trip efficiency; however, the high-potential photogenerated holes during the charge would degrade the electrolyte with side reactions and poor cycling performance. Herein, a synergistic interaction between a polyterthiophene photocatalyst and a redox mediator is employed in Li-O2 batteries. During the discharge, the voltage can be compensated by the photovoltage generated on the photoelectrode. Upon the charge with illumination, the photogenerated holes can be consumed by the oxidization of iodide ions, and thus the external circuit voltage is compensated by photogenerated electrons. Accordingly, a smaller bias voltage is needed for the semiconductor to decompose Li2 O2 , and the potential of photogenerated holes decreases. Finally, the round-trip efficiency of the battery reaches 97% with a discharge voltage of 3.10 V and a charge voltage of 3.19 V. The batteries show stable operation up to 150 cycles without increased polarization. This work provides new routes for light-assisted Li-O2 batteries with reduced overpotential and boosted efficiency.

The impact of neutralizing monoclonal antibodies on the outcomes of COVID-19 outpatients: A systematic review and meta-analysis of randomized controlled trials.

To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID-19). PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID-19 outpatients were included. The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID-19-related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19-0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17-0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05-0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64-1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19-0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID-19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.

SABA prescriptions and asthma management practices in patients treated by specialists in Taiwan: Results from the SABINA III study.

PURPOSE: Limited data exist on asthma medication patterns in Taiwan. The objectives of the SABINA III cross-sectional study in Taiwan were thus, to describe patient demographics and clinical features and estimate short-acting ß2-agonist (SABA) and inhaled corticosteroids (ICS) prescriptions per patient. METHODS: Patients (≥18 years) with asthma were classified by investigator-defined asthma severity per the 2017 Global Initiative for Asthma (GINA) recommendations. Data on asthma symptom control (per GINA 2017 recommendations), severe exacerbation history, and prescribed treatments in the 12 months before study visit were collected using electronic case-report forms. Analyses were descriptive. RESULTS: Overall, all 294 analyzed patients (mean [SD] age, 57.9 [15.6] years; female, 69%) were enrolled by specialists and had fully reimbursed healthcare. Most patients were classified with moderate-to-severe asthma (93.2%; GINA steps 3-5), were obese (53.4%) and nonsmokers (79.6%), reported high school or university and/or postgraduate education (61.9%), and had ≤2 comorbidities (89.1%). Mean (SD) asthma duration was 8.3 (10.0) years, with 37.8% of patients experiencing ≥1 severe exacerbation 12 months before the study visit. Overall, 62.2%, 26.2%, and 11.6% of patients had well-controlled, partly controlled, and uncontrolled asthma, respectively. Crucially, 19.3% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (overprescription). ICS, ICS + long-acting ß2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 6.5%, 97.3%, and 31.6% of patients, respectively. CONCLUSION: Despite treatment by specialists and fully reimbursed healthcare, findings indicate room for improvement in asthma control and SABA prescription practices in Taiwan, emphasizing the need to adhere to latest evidence-based guidelines.

Accurate Reconstruction of Mandibular Defects With Vascularized Bone Flaps Through Utilization of Mandible Space-Retention Guides.

PURPOSE: Comprehensive evaluation of the effects of using computer-aided design and space retention guide technology to reconstruct mandibular defects using vascularized autogenous bone flaps. METHOD: This study included 8 patients who received autogenous bone flaps (2 cases of vascularized fibula flaps and 6 cases of vascularized iliac flaps) for mandibular defect reconstruction at Peking University School and Hospital of Stomatology, from July 2018 to May 2021. All patients received digital surgery planning, computer aided design/computer aided manufacture, surgical guide technique for the removal of diseased bone segments, as well as vascularized fibular flap/iliac flap reconstruction. Three-dimensional deviations were analyzed after the operation. RESULT: The mandibular defects of all 8 patients were successfully reconstructed using the vascularized fibular flap/iliac bone flap. There were no serious complications at either the donor site or recipient site during our follow-up. The average three-dimensional deviation of all 8 patients was 1.92 mm, based on comparisons of preoperative design and actual postoperative computed tomography. CONCLUSION: Utilizing computer aided design/computer aided manufacture, we designed a new mandibular space-retention guide, which can accurately translate the preoperative digital design plan to real-time surgery with satisfactory accuracy and efficacy.

Bullous Parametric Response Map for Functional Localization of COPD.

Advanced bronchoscopic lung volume reduction treatment (BLVR) is now a routine care option for treating patients with severe emphysema. Patterns of low attenuation clusters indicating emphysema and functional small airway disease (fSAD) on paired CT, which may provide additional insights to the target selection of the segmental or subsegmental lobe of the treatments, require further investigation. The low attenuation clusters (LACS) were segmented to identify the scalar and spatial distribution of the lung destructions, in terms of 10 fractions scales of low attenuation density (LAD) located in upper lobes and lower lobes. The LACs of functional small airway disease (fSAD) were delineated by applying the technique of parametric response map (PRM) on the co-registered CT image data. Both emphysematous LACs of inspiratory CT and fSAD LACs on expiratory CT were used to derive the coefficients of the predictive model for estimating the airflow limitation. The voxel-wise severity is then predicted using the regional LACs on the co-registered CT to indicate the functional localization, namely, the bullous parametric response map (BPRM). A total of 100 subjects, 88 patients with mild to very severe COPD and 12 control participants with normal lung functions (FEV1/FVC % > 70%), were evaluated. Pearson's correlations between FEV1/FVC% and LAV%HU-950 of severe emphysema are - 0.55 comparing to - 0.67 and - 0.62 of LAV%HU-856 of air-trapping and LAV%fSAD respectively. Pearson's correlation between FEV1/FVC% and FEV1/FVC% predicted by the proposed model using LAD% of HU-950 and fSAD on BPRM is 0.82 (p < 0.01). The result of the Bullous Parametric Response Map (BPRM) is capable of identifying the less functional area of the lung, where the BLVR treatment is aimed at removing from a hyperinflated area of emphysematous regions.

SHP-1/STAT3-Signaling-Axis-Regulated Coupling between BECN1 and SLC7A11 Contributes to Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma.

Ferroptosis is a type of iron-dependent cell death pertaining to an excess of lipid peroxidation. It has been suggested that sorafenib-an anti-angiogenic medication for hepatocellular carcinoma (HCC)-induces ferroptosis, but the underlying mechanism for this remains largely unknown. We employed siRNA-mediated gene silencing to investigate the role of Src homology region 2 domain-containing phosphatase-1 (SHP-1), following sorafenib treatment, in cystine/glutamate-antiporter-system-Xc--regulated cystine uptake. Co-immunoprecipitation was also performed to examine the interactions between MCL1, beclin 1 (BECN1), and solute carrier family 7 member 11 (SLC7A11), which functions as the catalytic subunit of system Xc-. The results of this study showed that sorafenib enhanced the activity of SHP-1, dephosphorylated STAT3, downregulated the expression of MCL1 and, consequently, reduced the association between MCL1 and BECN1. In contrast, increased binding between BECN1 and SLC7A11 was observed following sorafenib treatment. The elevated interaction between BECN1 and SLC7A11 inhibited the activity of system Xc-, whereas BECN1 silencing restored cystine intake and protected cells from ferroptosis. Notably, ectopic expression of MCL1 uncoupled BECN1 from SLC7A11 and rescued cell viability by attenuating lipid peroxidation. The results revealed that ferroptosis could be induced in HCC via SHP-1/STAT3-mediated downregulation of MCL1 and subsequent inhibition of SLC7A11 by increased BECN1 binding.

A Chemoenzymatic Cascade Combining a Hydration Catalyst with an Amine Dehydrogenase: Synthesis of Chiral Amines.

The combination of biocatalysis and transition-metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co-catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process.

Clinical efficacy and safety of remdesivir in patients with COVID-19: a systematic review and network meta-analysis of randomized controlled trials.

OBJECTIVES: We performed a systematic review and network meta-analysis of randomized controlled trials (RCTs) to provide updated information regarding the clinical efficacy of remdesivir in treating coronavirus disease 2019 (COVID-19). METHODS: PubMed, Embase, Cochrane Library, clinical trial registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched for relevant articles published up to 18 November 2020. RESULTS: Five RCTs, including 13 544 patients, were included in this meta-analysis. Among them, 3839 and 391 patients were assigned to the 10 day and 5 day remdesivir regimens, respectively. Patients receiving 5 day remdesivir therapy presented greater clinical improvement than those in the control group [OR = 1.68 (95% CI 1.18-2.40)], with no significant difference observed between the 10 day and placebo groups [OR = 1.23 (95% CI 0.90-1.68)]. Patients receiving remdesivir revealed a greater likelihood of discharge [10 day remdesivir versus control: OR = 1.32 (95% CI 1.09-1.60); 5 day remdesivir versus control: OR = 1.73 (95% CI 1.28-2.35)] and recovery [10 day remdesivir versus control: OR = 1.29 (95% CI 1.03-1.60); 5 day remdesivir versus control: OR = 1.80 (95% CI 1.31-2.48)] than those in the control group. In contrast, no mortality benefit was observed following remdesivir therapy. Furthermore, no significant association was observed between remdesivir treatment and an increased risk of adverse events. CONCLUSIONS: Remdesivir can help improve the clinical outcome of hospitalized patients with COVID-19 and a 5 day regimen, instead of a 10 day regimen, may be sufficient for treatment. Moreover, remdesivir appears as tolerable as other comparators or placebo.

The effect of additional antimicrobial therapy on the outcomes of patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

BACKGROUND: The effect of additional antimicrobial agents on the clinical outcomes of patients with idiopathic pulmonary fibrosis (IPF) is unclear. METHODS: We performed comprehensive searches of randomized control trials (RCTs) that compared the clinical efficacy of additional antimicrobial agents to those of placebo or usual care in the treatment of IPF patients. The primary outcome was all-cause mortality, and the secondary outcomes were changes in forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and the risk of adverse events (AEs). RESULTS: Four RCTs including a total of 1055 patients (528 receiving additional antibiotics and 527 receiving placebo or usual care) were included in this meta-analysis. Among the study group, 402 and 126 patients received co-trimoxazole and doxycycline, respectively. The all-cause mortality rates were 15.0% (79/528) and 14.0% (74/527) in the patients who did and did not receive additional antibiotics, respectively (odds ratio [OR] 1.07; 95% confidence interval [CI] 0.76 to 1.51; p = 0.71). No significant difference was observed in the changes in FVC (mean difference [MD], 0.01; 95% CI - 0.03 to 0.05; p = 0.56) and DLCO (MD, 0.05; 95% CI - 0.17 to 0.28; p = 0.65). Additional use of antimicrobial agents was also associated with an increased risk of AEs (OR 1.65; 95% CI 1.19 to 2.27; p = 0.002), especially gastrointestinal disorders (OR 1.54; 95% CI 1.10 to 2.15; p = 0.001). CONCLUSIONS: In patients with IPF, adding antimicrobial therapy to usual care did not improve mortality or lung function decline but increased gastrointestinal toxicity.