Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Restructuring Electrolyte Solvation by a Partially and Weakly Solvating Cosolvent toward High-Performance Potassium-Ion Batteries.

Ether-based electrolytes are among the most important electrolytes for potassium-ion batteries (PIBs) due to their low polarization voltage and notable compatibility with potassium metal. However, their development is hindered by the strong binding between K+ and ether solvents, leading to [K+-solvent] cointercalation on graphite anodes. Herein, we propose a partially and weakly solvating electrolyte (PWSE) wherein the local solvation environment of the conventional 1,2-dimethoxyethane (DME)-based electrolyte is efficiently reconfigured by a partially and weakly solvating diethoxy methane (DEM) cosolvent. For the PWSE in particular, DEM partially participates in the solvation shell and weakens the chelation between K+ and DME, facilitating desolvation and suppressing cointercalation behavior. Notably, the solvation structure of the DME-based electrolyte is transformed into a more cation-anion-cluster-dominated structure, consequently promoting thin and stable solid-electrolyte interphase (SEI) generation. Benefiting from optimized solvation and SEI generation, the PWSE enables a graphite electrode with reversible K+ (de)intercalation (for over 1000 cycles) and K with reversible plating/stripping (the K||Cu cell with an average Coulombic efficiency of 98.72% over 400 cycles) and dendrite-free properties (the K||K cell operates over 1800 h). We demonstrate that rational PWSE design provides an approach to tailoring electrolytes toward stable PIBs.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis.

BACKGROUND: Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM: To analyze the clinical features and risk factors of IFD. METHODS: Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS: The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION: A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.

The involvement of SigmaR1K142 degradation mediated by ERAD in neural senescence linked with CdCl2 exposure.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.

Association between visceral obesity index and diabetes: a systematic review and meta-analysis.

CONTENT: The correlation between visceral obesity index (VAI) and diabetes and accuracy of early prediction of diabetes are still controversial. OBJECTIVE: This study aims to review the relationship between high level of VAI and diabetes, and early predictive value of diabetes. DATA SOURCES: The databases of PubMed, Cochrane, Embase, and Web of Science were searched until October 17, 2023. STUDY SELECTION: After adjusting for confounding factors, the original study on the association between VAI and diabetes was analyzed. DATA EXTRACTION: We extracted odds ratio (OR) between VAI and diabetes management after controlling for mixed factors, and the sensitivity, specificity and diagnostic four grid table for early prediction of diabetes. DATA SYNTHESIS: 53 studies, comprising 595,946 participants were included. The findings of the meta-analysis elucidated that in cohort studies, a high VAI significantly increased the risk of diabetes mellitus in males (OR = 2.83 (95% CI: 2.30-3.49)) and females (OR = 3.32 (95% CI: 2.48-4.45)). The ROC, sensitivity, and specificity of VAI for early prediction of diabetes in males were 0.64 (95% CI: 0.62-0.66), 0.57 (95% CI: 0.53-0.61), and 0.65 (95% CI: 0.61-0.69), respectively, and 0.67 (95% CI: 0.65-0.69), 0.66 (95% CI: 0.60-0.71), and 0.61 (95% CI: 0.57-0.66) in females, respectively. CONCLUSIONS: VAI is an independent predictor of the risk of diabetes, yet its predictive accuracy remains limited. In future studies, determine whether VAI can be utilized in conjunction with other related indicators to early predict the risk of diabetes, to enhance the accuracy of prediction of the risk of diabetes.

Global, regional, and national burden of atrial fibrillation/flutter related to metabolic risks over three decades: estimates from the global burden of disease study 2019.

AIMS: Atrial fibrillation/atrial flutter (AF/AFL) remains a significant public health concern on a global scale, with metabolic risks playing an increasingly prominent role. This study aimed to investigate comprehensive epidemiological data and trends concerning the metabolic risks related-AF/AFL burden based on the data from the Global Burden of Disease (GBD) study 2019. METHODS & RESULTS: The analysis of disease burden focused on numbers, age-standardized rates (ASR) of deaths, disability-adjusted life years (DALYs), and estimated annual percentage change (EAPC), while considering factors of age, sex, sociodemographic index (SDI), and locations. In 2019, there was a culmination of 137 179 deaths and 4 099 146 DALYs caused by metabolic risks related-AF/AFL worldwide, with an increase of 162.95% and 120.30% respectively from 1990. High and high-middle SDI regions predominantly carried the burden of AF/AFL associated with metabolic risks, while a shift towards lower SDI regions had been occurring. Montenegro had the highest recorded death rate (7.6 per 100 000) and DALYs rate (146.3 per 100 000). An asymmetrically inverted V-shaped correlation was found between SDI and deaths/DALYs rates. Moreover, females and the elderly exhibited higher AF/AFL burdens, and young adults (over 40 years old) also experienced an annual increase. CONCLUSIONS: The global AF/AFL burden related to metabolic risks has significantly increased over past three decades, with considerable spatiotemporal, gender-based, and age-related heterogeneity. These findings shed valuable light on the trends in the burden of metabolic risks related-AF/AFL, and offered insights into corresponding strategies.

Ileum excision partially reverses improvement of glucose metabolism in diabetic rats after biliopancreatic diversion with duodenal switch.

BACKGROUND: Bile acids can stimulate the secretion of glucagon-like peptide-1 (GLP-1) and be mostly reabsorbed in the ileum. OBJECTIVES: We aimed to investigate whether ileum excision could reverse the glucose improvement after biliopancreatic diversion with duodenal switch (BPD/DS). SETTING: Peking Union Medical College Hospital. METHODS: Thirty diabetic rats were randomly divided into the BPD/DS group, BPD/DS plus ileectomy (BDI) group, and control group. The fasting blood glucose, bile acids, and glucagon-like peptide-1(GLP-1) levels in plasma samples were analyzed. RESULTS: In postoperative week 20, the fasting blood glucose level in the BDI group was significantly higher than that in the BPD/DS group (11.5 ± 1.4 mmol/L versus 7.6 ± 1.0 mmol/L, P < .001), and the AUCOGTT value was also significantly higher than that in the BPD/DS group (2186.1 ± 237.2 mmol/L·min versus 1551.2 ± 136.9 mmol/L·min, P < .001). The plasma level of bile acids in the BDI group was lower than that in the BPD/DS group (P = .012) and was not significantly different from that in the control group (P = .629). The plasma level of GLP-1 in the BDI group was lower than that in the BPD/DS group (P = .009) and was not significantly different from that in the control group (P = .530). Moreover, the intestinal TGR5 expression in the BDI group was significantly lower than that in the BPD/DS group (P < .001). CONCLUSIONS: The results show that excision of the ileum can partially reverse the improvement in glucose metabolism after BPD/DS.

Protocol for isolating single species of bacteria with swarming ability from human feces.

Understanding the specific movements of bacteria isolated from human feces can serve as a novel diagnostic and therapeutic tool for inflammatory bowel disease. Here, we present a protocol for a microbial swarming assay and to isolate the bacteria responsible for swarming activity. We describe steps for identifying bacteria using MALDI-TOF mass spectrometry and whole-genome sequencing. We then detail procedures for validating findings by observing the same swarming phenotype upon reperforming the swarming assay. For complete details on the use and execution of this protocol, please refer to De et al.1.

Hsa_circ_0079875 functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression.

Circular RNA (circRNA) can influence the development of hepatocellular carcinoma (HCC) as a competitive endogenous RNA (ceRNA). However, there are still many circRNAs whose functions are unknown. Our research explores the role of a novel circRNA, hsa_circ_0079875, in HCC. The expression of hsa_circ_0079875 in HCC was verified by next-generation sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH). The distribution of hsa_circ_0079875 in HCC cells was investigated by RNA subcellular isolation and FISH assays. The functional effects on HCC proliferation, invasion, migration, cell cycle, and apoptosis were verified by overexpression and knockdown of hsa_circ_0079875. Moreover, xenograft mouse models and immunohistochemistry experiments were used to assess the function of hsa_circ_0079875 in vivo. Hsa_circ_0079875 was up-regulated in HCC tissues and mainly distributed in the cytoplasm. Higher hsa_circ_0079875 leads to larger tumor tissue, more microvascular invasion(MVI) and higher AFP levels, which in turn leads to a poor prognosis. Overexpression of hsa_circ_0079875 can promote the proliferation, migration, and invasion of HCC cells and inhibit apoptosis in vitro and in vivo. Knocking down hsa_circ_0079875 has the opposite effect. Sequencing and biological information predicted the target miRNA and mRNA of hsa_circ_0079875. Further bioinformatics and clinical correlation analysis revealed that hsa_circ_0079875 promote the malignant biological behaviors of HCC through hsa_circ_0079875/miR-519d-59/NRAS ceRNA net. Therefore, hsa_circ_0079875 can be a potential prognostic marker and therapeutic target for HCC.

Macromers for Encapsulating Perovskite Photovoltaics and Achieving High Stability.

Perovskite solar cells (pero-SCs) are highly unstable even under trace water. Although the blanket encapsulation (BE) strategy applied in the industry can effectively block moisture invasion, the commercial UV-curable adhesives (UVCAs) for BE still trigger power conversion efficiency deterioration, and the degradation mechanism remains unknown. For the first time, the functions of commercial UVCAs are revealed in BE-processed pero-SCs, where the small-sized monomer easily permeates to the perovskite surface, forming an insulating barrier to block charge extraction, while the high-polarity moiety can destroy perovskite lattice. To solve these problems, a macromer, named PIBA is carefully designed, by grafting two acrylate terminal groups on the highly gastight polyisobutylene and realizes an increased molecular diameter as well as avoided high-polarity groups. The PIBA macromer can stabilize on pero-SCs and then sufficiently crosslink, forming a compact and stable network under UV light without sacrificing device performance during the BE process. The resultant BE devices show negligible efficiency loss after storage at 85% relative humidity for 2000 h. More importantly, these devices can even reach ISO 20653:2013 Degrees of protection IPX7 standard when immersed in one-meter-deep water. This BE strategy shows good universality in enhancing the moisture stability of pero-SCs, irrespective of the perovskite composition or device structure.

Deciphering the removal of antibiotics and the antibiotic resistome from typical hospital wastewater treatment systems.

Hospital wastewater treatment systems (HWTSs) are a significant source and reservoir of antibiotic resistance genes (ARGs) and a crucial hub for transmitting ARGs from clinical to natural environments. However, there is a lack of research on the antibiotic resistome of clinical wastewater in HWTSs. In this study, we used metagenomics to analyze the prevalence and abundance of ARGs in five typical HWTSs. A total of 17 antibiotics from six categories were detected in the five HWTSs; ß-lactam antibiotics were found at the highest concentrations, with up to 4074.08 ng·L-1. We further found a total of 21 ARG types and 1106 subtypes of ARGs with the highest percentage of multi-drug resistance genes (evgS, msbA, arlS, and baeS). The most abundant last-resort ARGs were mcr, which were detected in 100 % of the samples. HWTSs effluent is a major pathway for the transmission of last-resort ARGs into urban wastewater networks. The removal of antibiotics, antibiotic-resistant bacteria, and ARGs from HWTSs was mainly achieved by tertiary treatment, i.e., chlorine disinfection, but antibiotics and ARGs were still present in the HWTSs effluent or even increased after treatment. Moreover, antibiotics and heavy metals (especially mercury) in hospital effluents can exert selective pressure for antibiotic resistance, even at low concentrations. Qualitative analyses based on metagenome-assembled genome analysis revealed that the putative hosts of the identified ARGs are widely distributed among Pseudomonas, Acidovorax, Flavobacterium, Polaromonas, and Arcobacter. Moreover, we further assessed the clinical availability of ARGs and found that multidrug ARGs had the highest clinical relevance values. This study provides new impulses for monitoring and removing antibiotics and ARGs in the hospital sewage treatment process.

Substrate-induced condensation activates plant TIR domain proteins.

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR-NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.

Heterogeneous Nucleating Agent for High-Boiling-Point Nonhalogenated Solvent-Processed Organic Solar Cells and Modules.

High-boiling-point nonhalogenated solvents are superior solvents to produce large-area organic solar cells (OSCs) in industry because of their wide processing window and low toxicity; while, these solvents with slow evaporation kinetics will lead excessive aggregation of state-of-the-art small molecule acceptors (e.g. L8-BO), delivering serious efficiency losses. Here, a heterogeneous nucleating agent strategy is developed by grafting oligo (ethylene glycol) side-chains on L8-BO (BTO-BO). The formation energy of the obtained BTO-BO; while, changing from liquid in a solvent to a crystalline phase, is lower than that of L8-BO irrespective of the solvent type. When BTO-BO is added as the third component into the active layer (e.g. PM6:L8-BO), it easily assembles to form numerous seed crystals, which serve as nucleation sites to trigger heterogeneous nucleation and increase nucleation density of L8-BO through strong hydrogen bonding interactions even in high-boiling-point nonhalogenated solvents. Therefore, it can effectively suppress excessive aggregation during growth, achieving ideal phase-separation active layer with small domain sizes and high crystallinity. The resultant toluene-processed OSCs exhibit a record power conversion efficiency (PCE) of 19.42% (certificated 19.12%) with excellent operational stability. The strategy also has superior advantages in large-scale devices, showing a 15.03-cm2 module with a record PCE of 16.35% (certificated 15.97%).

Detection and quantification of biogenic amines in cephalopod using dansyl chloride pre-column derivatization-HPLC and their production.

The accurate detection of biogenic amines (BAs) is an important means of ensuring the quality and safety of cephalopod seafood products. In this study, the pre-column derivatization of high-performance liquid chromatography (HPLC) was optimized using dansyl chloride (Dns-Cl) to detect BAs in octopus, cuttlefish, and squid. The reasons for the formation of BAs were investigated by assessing their decarboxylase activity and the rates of decomposition. The findings demonstrated that using Dns-Cl to optimize pre-column derivatization enabled the separation of nine different BAs. The detection limits ranged from 0.07 to 0.25 mg/L, and the results exhibited a high level of linearity (R2 ≥ 0.997). The decarboxylase activity and biodegradation rate positively correlated with the formation of BAs at temperatures below 0°C. Notably, the decarboxylase activity of octopus, cuttlefish, and squid exhibited a significant increase with prolonged storage time, and formyltransferase and carbamate kinase may be the key decarboxylase in cephalopod products. These findings serve as a valuable reference for further investigations into the mechanisms behind BAs production and the development of control technologies for BAs in cephalopod products. This study has successfully demonstrated the effectiveness of the Dns-Cl pre-column derivatization-HPLC method in accurately and efficiently detecting BAs in octopus, cuttlefish, and squid. Moreover, it highlights the influence of decarboxylase content and biodegradation rate on the formation of BAs. Importantly, this method can serve as a reference for detecting BAs in various seafood products.

Chiral Osmium(II)/Salox Species Enabled Enantioselective γ-C(sp3)-H Amidation: Integrated Experimental and Computational Validation For the Ligand Design and Reaction Development.

Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp3)-H functionalization, among which the Os(II)/Salox species is found to be the most efficient for precise stereocontrol in realizing the asymmetric C(sp3)-H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site-/enantioselective C(sp3)-H amidation in the γ-position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral γ-lactam products with good er values (up to 99 : 1) and diverse functionality (>35 examples). The unique performance advantage of the developed chiral Os(II)/Salox system in terms of the catalytic energy profile and the chiral induction has been further clarified by integrated experimental and computational studies.

Molecular regulatory mechanisms of staminate strobilus development and dehiscence in Torreya grandis.

Gymnosperms are mostly dioecious, and their staminate strobili undergo a longer developmental period than those of angiosperms. However, the underlying molecular mechanisms remain unclear. This study aimed to identify key genes and pathways involved in staminate strobilus development and dehiscence in Torreya grandis. Through weighted gene co-expression network analysis (WGCNA), we identified fast elongation-related genes enriched in carbon metabolism and auxin signal transduction, whereas dehiscence-related genes were abundant in alpha-linolenic acid metabolism and the phenylpropanoid pathway. Based on WGCNA, we also identified PHYTOCHROME-INTERACTING FACTOR4 (TgPIF4) as a potential regulator for fast elongation of staminate strobilus and 2 WRKY proteins (TgWRKY3 and TgWRKY31) as potential regulators for staminate strobilus dehiscence. Multiple protein-DNA interaction analyses showed that TgPIF4 directly activates the expression of TRANSPORT INHIBITOR RESPONSE2 (TgTIR2) and NADP-MALIC ENZYME (TgNADP-ME). Overexpression of TgPIF4 significantly promoted staminate strobilus elongation by elevating auxin signal transduction and pyruvate content. TgWRKY3 and TgWRKY31 bind to the promoters of the lignin biosynthesis gene PHENYLALANINE AMMONIA-LYASE (TgPAL) and jasmonic acid metabolism gene JASMONATE O-METHYLTRANSFERASE (TgJMT), respectively, and directly activate their transcription. Overexpression of TgWRKY3 and TgWRKY31 in the staminate strobilus led to early dehiscence, accompanied by increased lignin and methyl jasmonate levels, respectively. Collectively, our findings offer a perspective for understanding the growth of staminate strobili in gymnosperms.

The prognostic significance of right paratracheal lymph node dissection numbers in right upper lobe non-small cell lung cancer.

BACKGROUND: The number of dissected lymph nodes is closely related to the prognosis of patients with non-small cell lung cancer. This study explored the optimal number of right paratracheal lymph nodes dissected in right upper non-small cell lung cancer patients and its impact on prognosis. METHODS: Patients who underwent radical surgery for right upper lobe cancer between 2012 and 2017 were retrospectively enrolled. The optimal number of right paratracheal lymph nodes and the relationship between the number of dissected right paratracheal lymph nodes and the prognosis of right upper non-small cell lung cancer were analysed. RESULTS: A total of 241 patients were included. The optimal number of dissected right paratracheal lymph nodes was 6. The data were divided according to the number of dissected right paratracheal lymph nodes into groups RPLND + (≥ 6) and RPLND- (< 6). In the stage II and III patients, the 5-year overall survival rates were 39.0% and 48.2%, respectively (P = 0.033), and the 5-year recurrence-free survival rates were 32.8% and 41.8%, respectively (P = 0.043). Univariate and multivariate analyses revealed that among the stage II and III patients, ≥ 6 right paratracheal dissected lymph nodes was an independent prognostic factor for overall survival (HR = 0.53 95% CI 0.30-0.92 P = 0.025) and recurrence-free survival (HR = 1.94 95% CI 1.16-3.24 P = 0.011). CONCLUSIONS: Resection of 6 or more right paratracheal lymph nodes may be associated with an improved prognosis in patients with right upper non-small cell lung cancer, especially in patients with stage II or III disease.

SIRT7 promotes the proliferation and migration of anaplastic thyroid cancer cells by regulating the desuccinylation of KIF23.

OBJECTIVE: This study was designed to investigate the regulatory effects of kinesin family member (KIF) 23 on anaplastic thyroid cancer (ATC) cell viability and migration and the underlying mechanism. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the levels of KIF23 in ATC cells. Besides, the effects of KIF23 and sirtuin (SIRT) 7 on the viability and migration of ATC cells were detected using cell counting kit-8, transwell and wound healing assays. The interaction between SIRT7 and KIF23 was evaluated by co-immunoprecipitation (Co-IP) assay. The succinylation (succ) of KIF23 was analyzed by western blot. RESULTS: The KIF23 expression was upregulated in ATC cells. Silencing of KIF23 suppressed the viability and migration of 8505C and BCPAP cells. The KIF23-succ level was decreased in ATC cells. SIRT7 interacted with KIF23 to inhibit the succinylation of KIF23 at K537 site in human embryonic kidney (HEK)-293T cells. Overexpression of SIRT7 enhanced the protein stability of KIF23 in HEK-293T cells. Besides, overexpression of KIF23 promoted the viability and migration of 8505C and BCPAP cells, which was partly blocked by silenced SIRT7. CONCLUSIONS: SIRT7 promoted the proliferation and migration of ATC cells by regulating the desuccinylation of KIF23.

Recent Progress in Dopant-Free and Green Solvent-Processable Organic Hole Transport Materials for Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transport layers (HTLs) are crucial in enhancing perovskite solar cells (pero-SCs). Nevertheless, conventional processing of these HTL materials involves using toxic solvents, which gives rise to substantial environmental concerns and renders them unsuitable for large-scale industrial production. Consequently, there is a pressing need to develop dopant-free HTL materials processed using green solvents to facilitate the production of high-performance pero-SCs. Recently, several strategies have been developed to simultaneously improve the solubility of these materials and regulate molecular stacking for high hole mobility. In this review, a comprehensive overview of the methodologies utilized in developing dopant-free HTL materials processed from green solvents is provided. First, the study provides a brief overview of fundamental information about green solvents and Hansen solubility parameters, which can serve as a guideline for the molecular design of optimal HTL materials. Second, the intrinsic relationships between molecular structure, solubility in green solvents, molecular stacking, and device performance are discussed. Finally, conclusions and perspectives are presented along with the rational design of highly efficient, stable, and green solvent-processable dopant-free HTL materials.

Alterations of White Matter Connectivity in Adults with Essential Hypertension.

Purpose: To explore the topology of the white matter network in individuals with essential hypertension by graph theory. Patients and Methods: T1-weighted image and diffusion tensor imaging (DTI) data from 43 patients diagnosed with essential hypertension (EHT) and 33 individuals with normotension (healthy controls, HCs) were incorporated in this cross-sectional study. Furthermore, structural networks were constructed by graph theory to calculate whole brain network characteristics and intracerebral node characteristics. Results: Both EHT and HC groups displayed small-worldness in their structural networks. The area under the curve (AUC) of the small-worldness coefficient (σ) was higher in the EHT group compared to the HC group, whereas the AUC of assortativity was lower in the EHT group in contrast to the HC group. The nodal clustering coefficient (CP) and local efficiency (Eloc) of the EHT group decreased in the right dorsolateral superior frontal gyrus and the left medial superior frontal gyrus. These values increased in the left anterior cingulate and paracingulate gyrus. Furthermore, weight and body mass index (BMI) were positively correlated with σ. Conclusion: The EHT group showed brain network separation and integration dysfunction. Weight and BMI were positively correlated with σ. The data acquired in this investigation implied that altered structural connectivity in the prefrontal region may be a potential neuroimaging marker in EHT patients.