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Yun-Ming Tian,1 Lei Zeng,2 Yu-Hong Lan,1 Xia Yuan,3 Li Bai,1,* Fei Han4,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Medical Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre; State Key Laboratory of Oncology in South China; Collaborative Innovation Centre for Cancer Medicine, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li BaiDepartment of Radiation Oncology, Hui Zhou Municipal Central Hospital, No. 41 Eling North Road, Huizhou, Guangdong, People’s Republic of ChinaEmail bailihuizhou@126.comFei HanDepartment of Radiation Oncology, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, People’s Republic of ChinaEmail hanfeisysucc@126.comObjective: To investigate the prognostic value of cervical node features in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) and build a prognostic nomogram to predict the long-term survival.Methods: In this study, 1752 patients after IMRT from 2008 to 2011 were recruited. The clinical and laboratory characteristics and the nodal features including the nodal number, maximum dimension diameter, extranodal extension (ENE), and cervical node necrosis (CNN) were retrospective analyzed. Univariate Cox and multivariate proportional hazard regression models were used to test the prognostic value of nodal features. Prognostic nomograms were established to predict survival.Results: The 10-year distant metastases-free survival (DMFS) and disease-specific survival (DSS) rates were 86.5% and 80.8%, respectively. Multivariate analysis showed that age, sex, lactate dehydrogenase (LDH), CNN, ENE, T stage, and N stage were independent factors for DSS. Two nomograms—nomogram A (without nodal features) and nomogram B (with nodal features)—were built. The calibration curve for the probability of DSS showed good agreement between prediction by nomogram and the actual observation. The C-index of nomogram B was higher than that for nomogram A in predicting DSS (0.708 vs 0.676, P< 0.01).Conclusion: The nodal features including ENE and CNN were negative prognostic factors for NPC, and the prognostic nomogram incorporating the nodal features was more accurate in predicting survival than the nomogram without nodal features.Keywords: nodal features, extranodal extension, nodal necrosis, nasopharyngeal carcinoma, prognostic value

Backgruound: The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies., Methods: MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function., Results: Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores., Conclusion: Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Peroxynitrite (ONOO - ) is a transient and reactive oxidant with significant roles in numerous biological processes. Research has established a correlation between excessive mitochondrial ONOO - production and various diseases. As such we developed a mitochondria-targeting, fluorescence-based ratiometric probe using a boronate group for ONOO - recognition and coumarin as the fluorophore. The probe exhibited a 615 nm far-red emission, and a new fluorescence emission at 475 nm developed upon adding ONOO - .The probe possessed high sensitivity and selectivity for ONOO - detection with distinct ratiometric fluorescent output and a low detection limit of 11 nM. Significantly, Probe 1 could monitor ONOO - level fluctuations in biological systems due to its superior spectral properties and low toxicity. Notably, probe 1 has been effectively used for imaging in live HepG2 cells, zebrafish, Arabidopsis thaliana, and liver injury mouse tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality. Methods: This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk. Results: A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P <0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI : 1.63-3.99). Conclusion: The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with β-(1,3)-Glcp as the main chain and β-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality. Methods: A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality. Results: The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio ( HR )=1.68, 95% CI : 1.44-1.94] and an increased risk of CVD mortality by 1.56 times ( HR =1.56, 95% CI : 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P >0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P <0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P <0.05). Conclusions: The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.

This commentary highlighted the current knowledge about novel DLL3-targeting agents for refractory small cell lung cancer., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s). Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Water can accelerate a variety of organic reactions far beyond the rates observed in classical organic solvents. However, using pure water as a solvent introduces solubility constraints that have limited the applicability of efficient photochemistry in particular. We report here the formation of aggregates between pairs of arenes, heteroarenes, enamines, or esters with different electron affinities in an aqueous medium, leading to an oil-water phase boundary through substrate melting point depression. The active hydrogen atoms in the reactants engage in hydrogen bonds with water, thereby accelerating photochemical reactions. This methodology realizes appealingly simple conditions for aqueous coupling reactions of complex solid molecules, including complex drug molecules that are poorly soluble in water.

Postsynthetic diversification of peptides through selective modification of endogenous amino acid side chains has enabled significant advances in peptide drug discovery while expanding the biological and medical chemistry space. However, current tools have been focused on the modification of reactive polar and ionizable side chains, whereas the decoration of aromatic systems (e.g., the N (in) of the tryptophan) has been a long-standing challenge. Here, we introduce metallaphotocatalysis in solid-phase peptide synthesis for the on-resin orthogonal N -arylation of relevant tryptophan-containing peptides. The protocol allows the chemoselective introduction of a new C(sp 2 )-N bond at the N (in) of tryptophan in biologically active protected peptide sequences in the presence of native redox-sensitive side chains. The fusion of metallaphotocatalysis with solid-phase peptide synthesis opens new perspectives in diversifying native amino acid side chains.

As a major neuron type in the brain, the excitatory neuron (EN) regulates the lifespan in C. elegans. How the EN acquires senescence, however, is unknown. Here, we show that growth differentiation factor 11 (GDF11) is predominantly expressed in the EN in the adult mouse, marmoset and human brain. In mice, selective knock-out of GDF11 in the post-mitotic EN shapes the brain ageing-related transcriptional profile, induces EN senescence and hyperexcitability, prunes their dendrites, impedes their synaptic input, impairs object recognition memory and shortens the lifespan, establishing a functional link between GDF11, brain ageing and cognition. In vitro GDF11 deletion causes cellular senescence in Neuro-2a cells. Mechanistically, GDF11 deletion induces neuronal senescence via Smad2-induced transcription of the pro-senescence factor p21. This work indicates that endogenous GDF11 acts as a brake on EN senescence and brain ageing., (© 2023. The Author(s).)

Background: Previous studies on associations of perceived stress with poor memory performance in older adults showed inconsistent results. We examined the prospective associations of perceived stress with memory decline using data from Guangzhou Biobank Cohort Study (GBCS)., Methods: Perceived stress was measured by the Perceived Stress Scale (PSS) at baseline (2003-2006), with greater scores indicating greater stress. Memory function was measured by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT), with greater scores indicating better performance, at baseline and follow-up (2008-2012) examinations, analyzed as mean annual change in scores., Results: 9656 participants (72 % women) with mean age 61.6 (standard deviation = 6.4) years were included. During an average of 4.4 years of follow-up, after adjusting for confounders, each one-point greater PSS score was associated with mean annual decline in DWRT scores (β (95 % CI) = -0.005 (-0.008 to -0.002)). Greater Perceived Helplessness (PH) scores, but not Perceived Self-efficacy scores, was associated with greater mean annual decline in DWRT and IWRT scores (β (95 % CI) = -0.005 (-0.009 to -0.001) and - 0.012 (-0.018 to -0.005), respectively), and similar patterns were observed in five out of seven PH items (βs from -0.02 to -0.07). Interaction analysis showed that the association of greater PSS with greater decline in DWRT scores was observed only in those with low family income (β (95 % CI) = -0.08 (-0.13 to -0.04), P for interaction = 0.03)., Conclusions: Greater perceived stress was associated with a greater decline in delayed recall memory, especially in those with low family income., Competing Interests: Declaration of competing interest The authors declared that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Background: Current guidelines stress the importance of exercise, especially multicomponent exercise to older adults with chronic conditions., Aim: To critically synthesise evidence that evaluates the effects of multicomponent exercise on quality of life, depression and anxiety after stroke., Design: Systematic review and meta-analysis followed the PRISMA 2020 statement., Methods: A systematic search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL and PsycINFO from inception to 12 June 2023 was performed. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Meta-analyses were conducted using Review Manager 5.4 and narrative syntheses were adopted whenever meta-analysis was inappropriate. The overall certainty of the evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Results: Of 15,351 records identified, nine were eligible and data were available for seven randomised controlled trials, three of which were identified as having a high risk of bias, one as low risk, and five as having some concerns. Subgroup pooled analyses indicated that multicomponent exercise engaged in longer exercise sessions (>60 min) was effective in improving quality of life immediately post-intervention and through 3-6 months post-intervention. However, multicomponent exercise did not significantly affect depression and anxiety., Conclusions: Multicomponent exercise with longer duration of exercise sessions has promising effects on both short- to medium-term quality of life among stroke survivors., Patient or Public Contribution: This does not apply to our work as it is a review paper., Relevance to Clinical Practice: Healthcare providers could consider encouraging the patients to participate in multicomponent exercise sessions for more than 60 min. It is important to note that stroke survivors should be supervised by trained personnel at the beginning of the training., Registration: The protocol was registered on PROSPERO., (© 2023 John Wiley & Sons Ltd.)

Background: Breast cancer is the most common malignancy in female patients. In recent years, more and more studies have focused on how to improve the appearance and the quality of life for patients. This study aimed to compare the oncologic safety, aesthetic results, and upper extremity function between single-port insufflation endoscopic nipple-sparing mastectomy (SIE-NSM) and conventional open mastectomy (C-OM) in early-stage breast cancer treatment., Methods: In our retrospective cohort, 285 patients with stage I and II breast cancer were categorized into the SIE-NSM group (n=71) and the C-OM group (n=214). We assessed local recurrence, distant metastasis, and upper extremity function across the two groups. The BREAST-Q scale was employed to analyze differences in aesthetic results, psychosocial well-being, and sexual health. The risk of local recurrence was evaluated using multivariable binary logistic regression, while a multivariable linear regression model gauged upper extremity function and aesthetic outcomes., Results: Local recurrence rates between the two groups were statistically similar (1/71, 1.4% for SIE-NSM vs. 2/214, 0.9% for C-OM, P=0.735), as confirmed by the multivariable binary logistic regression analysis. Neither group exhibited distant metastases. The SIE-NSM group demonstrated higher scores in satisfaction with breasts, chest wellness, psychosocial health, and sexual well-being (P<0.001). The SIE-NSM group also exhibited superior outcomes regarding chest wall/breast pain, shoulder mobility, and daily arm usage (P<0.001). No subcutaneous effusion was reported in the SIE-NSM group, whereas the C-OM group had a 10.7% incidence rate (P=0.004)., Conclusions: SIE-NSM offers comparable oncologic safety to C-OM but provides enhanced satisfaction regarding breast appearance, physical comfort, psychosocial health, sexual health, and improved upper extremity functionality. Consequently, this innovative approach is a suitable surgical alternative for treating early-stage breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-23-148/coif). The authors have no conflicts of interest to declare., (2023 Gland Surgery. All rights reserved.)

Currently, micro- and nanoplastics are the most concerning pollutants, which have been confirmed to exist in every stage of drinking water treatment process. Micro- and nanoplastics in drinking water have large specific surface areas, which could adsorb inorganic matter, organic matter, and microorganisms, thereby increasing their risk to human health. The adsorption and agglomeration behavior of micro- and nanoplastics on typical pollutants is called the "colloid pump effect." Focused on the micro- and nanoplastics in drinking water, the occurrence, colloid pump effect, and toxic effect on the human body and the effect of colloid pumps on the removal of micro- and nanoplastics were summarized and described. The results revealed that micro- and nanoplastics existed widely in source water, treated water, pipe network water, and tap water. The colloid pump effect of micro- and nanoplastics promoted their agglomeration with inorganic matter, organic matter, and microorganisms, which not only intensified the toxic effect of micro- and nanoplastics but also affected the removal effect. There were different viewpoints on the effect of coagulation and sedimentation on the removal of micro- and nanoplastics, and the removal effect of sand filters was limited. The advanced treatment was an efficient process to remove micro- and nanoplastics with a particle size smaller than 5 μm. The removal rate of micro- and nanoplastics could be effectively improved by exploring the mechanism of the colloid pump effect and its initiation conditions. Finally, from the perspective of the drinking water treatment process and colloid pump effect, the control of micro- and nanoplastics in drinking water was prospected in order to provide reference for reducing the occurrence and toxicity of micro- and nanoplastics in drinking water, ensuring drinking water quality safety and human health.

Exploring highly efficient blue-emissive lead-free halide materials is a significant and challenging objective in the study of luminescent materials. This study reports the synthesis of a new zero-dimensional (0D) hybrid zinc halide of [CYP]ZnBr 4 (CYP = 1-cyclohexylpiperazine) containing an isolated [ZnBr 4 ] 2- tetrahedron. [CYP]ZnBr 4 exhibits strong blue light emission with a high photoluminescence quantum yield (PLQY) of 79.22%, surpassing all previously reported 0D zinc halide counterparts. According to the theoretical and experimental studies, the blue light emission is attributed to intrinsic self-trapped excitons resulting from strong electron-phonon coupling and structural deformation. Importantly, [CYP]ZnBr 4 demonstrates excellent structural and luminescence stability toward high temperatures (180 °C) over at least half a month. High luminescence efficiency and stability enable [CYP]ZnBr 4 to be an efficient blue phosphor to fabricate white light-emitting diodes (LEDs), which produces high-quality white light with a color rendering index (CRI) of 93.1 and a correlated color temperature (CCT) of 5304 K, closely resembling natural sunlight. This white LED also exhibits consistent performance and stability across different drive currents, suggesting the potential for high-power optoelectronic applications. Overall, this study paves the way for the utilization of 0D hybrid halides in advanced solid-state lighting applications.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target., (© 2023. Springer Nature Limited.)

In animals, adaptation to changes in cellular oxygen levels is coordinated largely by 2-oxoglutarate-dependent prolyl-hydroxylase domain (PHD) dioxygenase family members, which regulate the stability of their hypoxia-inducible factor (HIF) substrates to promote expression of genes that adapt cells to hypoxia. Recently, 2-aminoethanethiol dioxygenase (ADO) was identified as a novel O 2 -sensing enzyme in animals. Through N-terminal cysteine dioxygenation and the N-degron pathway, ADO regulates the stability of a set of non-transcription factor substrates; the regulators of G-protein signaling 4, 5. and 16 and interleukin-32. Here, we set out to compare and contrast the in cellulo characteristics of ADO and PHD enzymes in an attempt to better understand their co-evolution in animals. We find that ADO operates to regulate the stability of its substrates rapidly and with similar O 2 -sensitivity to the PHD/HIF pathway. ADO appeared less sensitive to iron chelating agents or transition metal exposure than the PHD enzymes, possibly due to tighter catalytic-site Fe 2+ coordination. Unlike the PHD/HIF pathway, the ADO/N-degron pathway was not subject to feedback by hypoxic induction of ADO, and induction of ADO substrates was well sustained in response to prolonged hypoxia. The data also reveal strong interactions between proteolytic regulation of targets by ADO and transcriptional induction of those targets, that shape integrated cellular responses to hypoxia. Collectively, our comparative analysis provides further insight into ADO/N-degron-mediated oxygen sensing and its integration into established mechanisms of oxygen homeostasis., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Hypochlorite (ClO - ) is a ROS that plays a crucial role in the immune system in the body. As the largest organelle in the cell, the endoplasmic reticulum (ER) manages various life activities. Thus, a simple hydrazone-based probe was designed, which provided a fast turn-on fluorescent response toward ClO - . With a terminal p-toluenesulfonamide group as the endoplasmic reticulum (ER)-specific site, probe 1 was mainly accumulated at ER of living cells, and could be used for imaging endogenous and exogenous HClO in cells and zebrafishes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: To establish an animal model of delayed intravenous resuscitation following seawater immersion after hemorrhagic shock (HS)., Methods: Adult male SD rats were randomly divided into three groups: group NI (HS with no immersion), group SI (HS with skin immersion), and group VI (HS with visceral immersion). Controlled HS in rats was induced by withdrawing 45% of the calculated total blood volume within 30 min. In SI group, immediately after blood loss, 0.5 cm below the xiphoid process was immersed in artificial seawater, at (23 ± 1) °C, for 30 min. In VI group, the rats were performed by laparotomy and the abdominal organs were immersed in (23 ± 1) °C seawater for 30 min. Two hours after seawater immersion, the extractive blood and lactated Ringer's solution were delivered intravenously. The mean arterial pressure (MAP), lactate, and other biological parameters were investigated in different time points. The survival rate of 24 h after HS was recorded., Results: After seawater immersion following HS, MAP and abdominal viscera blood flow decreased significantly, and the plasma levels of lactate and the organ function parameters were increased than the baseline. The above changes in VI group were more serious than those in SI and NI group, especially in myocardial and small intestine damage. The hypothermia, hypercoagulation, and metabolic acidosis were also observed after seawater immersion; the injury was more severely in VI group than that of SI group. However, the plasma levels of sodium, potassium, chlorine, and calcium in VI group were significantly higher than those before injury and in the other two groups. In the VI group, the level of plasma osmolality in instant, 2 h, and 5 h after immersion was 111%, 109%, and 108% of the SI group, respectively, all P < 0.01. The 24-h survival rate of VI group was 25%, which was significantly lower than that of SI group (50%) and NI group (70%), P < 0.05., Conclusions: The model fully simulated the key damage factors and field treatment conditions, reflected the effects of low temperature and hypertonic damage caused by seawater immersion on the severity and prognosis of naval combat wounds, and provided a practical and reliable animal model for the study of field treatment technology of marine combat shock., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Much progress has been made toward generating analogs of early embryos, such as gastruloids and embryoids, in vitro. However, methods for how to fully mimic the cell movements of gastrulation and coordinate germ-layer patterning to induce head formation are still lacking. Here, we show that a regional Nodal gradient applied to zebrafish animal pole explant can generate a structure that recapitulates the key cell movements of gastrulation. Using single-cell transcriptome and in situ hybridization analysis, we assess the dynamics of the cell fates and patterning of this structure. The mesendoderm differentiates into the anterior endoderm, prechordal plate, notochord, and tailbud-like cells along an anterior-posterior axis, and an anterior-posterior-patterned head-like structure (HLS) progressively forms during late gastrulation. Among 105 immediate Nodal targets, 14 genes contain axis-induction ability, and 5 of them induce a complete or partial head structure when overexpressed in the ventral side of zebrafish embryos., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C-C or C-S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

As an emerging pollutant of global concern, microplastics (plastics with size<5 mm) and heavy metals are widely found in freshwater environments. Microplastics migrate easily, are difficult to degrade, and have large specific surface areas. They can enrich a variety of pollutants such as heavy metals and greatly increase their potential harm to the environment and ecology. Firstly, the special environmental behavior of microplastics carrying heavy metals and migrating together in freshwater environments was defined as the "Trojan-horse effect." Then, the Trojan-horse effect and its mechanism of microplastics and heavy metals in the freshwater environment were summarized and expounded from four aspects:the source and distribution of microplastics in the freshwater environment, the enrichment effect of microplastics on heavy metals, the impact of microplastics and the heavy metal Trojan-horse effect on its migration behavior, and the biological impact of microplastics and the heavy metal Trojan-horse effect. The results showed that, as a wide range of non-point source pollutants, microplastics widely existed in freshwater environments. In freshwater environments, the adsorption degree of single metals was different in different environments. It was mainly affected by microplastics, metals, and environmental factors. There was competitive adsorption in the presence of multiple metal ions. The Trojan-horse effect of microplastics and heavy metals could also affect their co-transport behavior. The Trojan-horse effect of microplastics and heavy metals in the freshwater environment frequently exacerbated their toxicity to aquatic organisms. This study provides references for comprehensively understanding the Trojan-horse effect and its mechanism in microplastics and heavy metals in the freshwater environment, which could effectively reduce the ecological risk and impact on human health of microplastics and heavy metals in the freshwater environment.

Background: Previous studies on associations of alcohol use with memory decline showed inconclusive results. We examined these associations using longitudinal data from the Guangzhou Biobank Cohort Study (GBCS) and explored whether these associations varied by sex and age group., Methods: Memory function was assessed by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT) at both baseline (2003-2008) and follow-up (2008-2012) examinations, expressed as the mean annual change and mean annual rate of change in scores. Memory cognitive impairment was defined by DWRT scores of less than 4. Multivariable linear regression models and restricted cubic spline were used for data analysis., Results: Of 14,827 participants without memory cognitive impairment at baseline, 90.2% were never or occasional drinkers, 5% moderate drinkers, 1.5% excessive drinkers, and 3.3% former drinkers. The mean (standard deviation) age was 60.6 (6.6) years old. During an average of 4.1 years follow-up, 1000 (6.7%) participants developed memory cognitive impairment. After adjusting for confounders, compared with never or occasional drinkers, moderate and excessive drinkers had significant decline in DWRT scores (β, 95% confidence interval (CI) = -0.04 (-0.08 to -0.01), and - 0.07 (-0.14 to 0.01), respectively), and IWRT scores (β, 95% CI = -0.10 (-0.19 to -0.01), and - 0.15 (-0.30 to 0.01), respectively) annually. With respect to the mean annual rate of change, moderate and excessive drinkers also showed greater decline in DWRT scores (β, 95% CI = -1.02% (-1.87% to -0.16%), and - 1.64% (-3.14% to -0.14%), respectively). The associations did not vary by sex and age group (all P values for interaction ≥ 0.10)., Conclusion: Compared to never or occasional alcohol use, moderate and excessive alcohol users had greater memory decline and the associations did not vary by sex and age group., (© 2022. The Author(s).)

Background: Orelabrutinib is a novel, small molecule, selective irreversible Bruton tyrosine kinase inhibitor. The purpose of this study was to evaluate the efficacy and safety of orelabrutinib in patients with relapsed or refractory Waldenström's macroglobulinemia (R/R WM)., Methods: This is a prospective, multicenter study of orelabrutinib in patients with WM who had at least one prior line of treatment. Orelabrutinib was administered orally at a daily dose of 150 mg until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR) assessed by the Independent Review Committee (IRC) according to IWWM-6. This study is registered with ClinicalTrials.gov, NCT04440059. This trial was also registered on Center for Drug Evaluation (www.chinadrugtrials.org.cn) in March 2019, with a number of CTR2019036., Findings: Between August 2019 and December 2020, 66 R/R WM patients were assessed for eligibility. Forty-seven eligible patients were evaluated for efficacy at a median follow-up of 16.4 months (interquartile range: 12.5, 19.5). As assessed by IRC, the MRR was 80.9%, and the overall response rate was 89.4%. The median time to at least a minor response was 1.9 months. The PFS rates was 89.4% at 12 months. For patients with MYD88 L265P / CXCR4 NEG , MYD88 L265P / CXCR4 S338X , and MYD88 NEG / CXCR4 NEG mutations, the MRRs were 84.6%, 100%, and 25.0%. Most adverse events were Grades 1 or 2 (91.0%). The common grade 3 or higher adverse events occurring were neutropenia (10.6%), thrombocytopenia (6.4%), and pneumonia (4.3%). Serious adverse events (SAE) occurred in 10 patients (21.3%). One treatment-related death was reported (hepatitis B reactivation)., Interpretation: Orelabrutinib has shown good efficacy and manageable safety profiles in patients with R/R WM., Funding: InnoCare Pharma., Competing Interests: DBZ, XXC, JJ, ZZF, SHY, WLZ, ZMS, WY, DJL, GHC, JDH, TL, YPS, BX, ZMZ, WX, and MZZ declare no competing interests. YMT, BZ, and RBZ are employees of InnoCare Pharma., (© 2022 The Author(s).)

Endergonic photocatalysis is the use of light to perform catalytic reactions that are thermodynamically unfavourable. While photocatalysis has become a powerful tool in facilitating chemical transformations, the light-energy efficiency of these processes has not gathered much attention. Exergonic photocatalysis does not take full advantage of the light energy input, producing low-energy products and heat, whereas endergonic photocatalysis incorporates a portion of the photon energy into the reaction, yielding products that are higher in free energy than the reactants. Such processes can enable catalytic, atom-economic syntheses of reactive compounds from bench-stable materials. With respect to environmental friendliness and carbon neutrality, endergonic photocatalysis is also of interest to large-scale industrial manufacturing, where better energy efficiency, less waste and value addition are highly sought. We therefore assess here the thermochemistry of several classes of reported photocatalytic transformations to showcase current advances in endergonic photocatalysis and point to their industrial potential., (© 2022. Springer Nature Limited.)

Objective: To study the protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats and explore the regulatory mechanism of toll-like receptors 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in this process. Methods: Sixty male SD rats were randomly divided into control group (C), model group (M), low-dose Lycium ruthenicum Murr. juice group (LLM), medium-dose Lycium ruthenicum Murr. juice group (MLM) and high-dose Lycium ruthenicum Murr. juice group (HLM), 12 rats in each group. The group M, LLM, MLM and HLM were treated with 20 ml/kg (8 g/(kg·d)) ethanol (400 g/L) intragastrically and the gavage was divided into two sessions, group C was treated with an equal volume of distilled water at the same time point. Four hours before the first alcohol gavage session, rats in each dose group of Lycium ruthenicum Murr. juice were administered with 2.4, 4.8, 9.6 ml/(kg·d) Lycium ruthenicum Murr. juice respectively, and the other groups were given equal volume of distilled water at the corresponding time points. Four weeks later, the rats were sacrificed 24 hours after the end of the last experiment, blood and liver were collected. The liver index was calculated. The morphology of the liver was observed by HE staining. The expressions of hepatic TLR4, p38 MAPK and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were detected by immunohistochemistry. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The levels of hepatic tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-10 (IL-10) and interleukin-18 (IL-18) were detected by enzyme linked immunosorbent assay. Results: Compared with group C, the alcoholic liver injury model was established successfully in Group M. Compared with group M, related indicators in each dose group of Lycium ruthenicum Murr. juice were improved, the improvement of hepatic morphology in group HLM was the most significant, the liver index, the levels of serum ALT, AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-1β, IL-18 were decreased ( P ＜ 0.05 or P ＜0.01), while the level of hepatic IL-10 was increased ( P ＜0.01). Comparison among the dose groups of Lycium ruthenicum Murr. juice, the levels of liver index, serum AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-18 in HLM were lower than those in LLM ( P ＜0.05 or P ＜0.01); the level of hepatic IL-10 in HLM was higher than that in LLM and MLM ( P ＜0.05 or P ＜0.01); the other indicators in each dose group had no statistical difference ( P ＞0.05). Conclusion: Lycium ruthenicum Murr. juice can improve the inflammatory stress by regulating TLR4/p38 MAPK signaling pathway, relieve alcoholic liver injury in rats, and the effect of high-dose group is better than the others.

Objectives: The aim of this study was to characterise the whole genome sequence of a multidrug-resistant (MDR) Proteus mirabilis strain ChSC1905 isolated from a swine farm in China., Methods: The genome was sequenced by Illumina NovaSeq and Oxford Nanopore platforms, and it was assembled via Canu v.1.5. The acquired antimicrobial resistance genes (ARGs) were identified by ResFinder. A conjugation experiment was carried out to determine the mobilisation of integrative and conjugative element., Results: Strain ChSC1905 exhibited a MDR phenotype. The genome of strain ChSC1905 was 4 038 038 bp in length with a GC content of 39.1%, which contained 3645 coding sequences and 110 RNA genes. A total of 23 acquired ARGs were identified, among which 21 ARGs including the clinically important resistance genes bla CTX-M-65 , cfr, fosA3, and aac(6')-Ib-cr were located on a SXT/R391 integrative and conjugative element (ICE). BLAST analysis showed that this new SXT/R391-family ICE (ICEPmiChnChSC1905 of 143 689 bp) was involved in sequence inversion mediated by ISVsa3 and genetic rearrangement mediated by IS26, and it could be transferred to E. coli EC600., Conclusion: In this study, we report the genome sequence of MDR P. mirabilis strain ChSC1905 that harboured a novel SXT/R391-family ICE (ICEPmiChnChSC1905) involved in genetic rearrangement in China, which promotes the diversity of ICE and should receive more attention., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Our previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) protects vascular endothelium function through ameliorating autophagy in mesenteric arteries of metabolic syndrome (MS) rats. This study aimed to investigate the role of adenosine mono-phosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling in CIHH effect. Six-week-old male Sprague-Dawley rats were divided into control (CON), MS model, CIHH treatment (CIHH), and MS + CIHH groups. Serum pro-inflammatory cytokines were measured. The endothelium dependent relaxation (EDR), endothelial ultrastructure and autophagosomes were observed in mesenteric arteries. The expression of phosphor (p)-AMPKα, p-mTOR, autophagy-related and endoplasmic reticulum stress-related proteins, p-endothelial nitric oxide synthase, and cathepsin D were assayed. In MS rats, pro-inflammatory cytokines were increased, EDR was attenuated, and endothelial integrity was impaired. In addition, the expression level of p-AMPKα and cathepsin D was down-regulated, but the level of p-mTOR was up-regulated. While in MS + CIHH rats, all aforementioned abnormalities were ameliorated, and the beneficial effect of CIHH was cancelled by AMPKα inhibitor. In conclusion, AMPK-mTOR signaling pathway participates in the protection of CIHH on vascular endothelium of MS rats.

We report a simple protocol for the transition metal-free, visible-light-driven conversion of 1,3-diketones to tetra-substituted furan skeleton compounds in carbon dioxide (CO 2 ) atmosphere under mild conditions. It was found that CO 2 could be incorporated at the diketone enolic OH position, which was key to enabling the cleavage of a C-O bond during the rearrangement of a cyclopropane intermediate. This method allows for the same-pot construction of two isomers of the high-value tetra-substituted furan scaffold. The synthetic scope and preliminary mechanistic investigations are presented., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We aim to describe a technique for intraocular lens (IOL) implantation with suture clamping for aphakic capsules. This prospective, noncomparative, interventional case study included three eyes of three patients with an aphakic capsule after vitrectomy, in which the IOL was clamped by suturing. The suturing procedure was transconjunctival or subconjunctival performed without scleral flaps. The IOLs were implanted without difficulty, and visual acuity improved after IOL implantation. There were no severe complications, and the position of each IOL remained correct through 18 months of follow-up. The present technique is straightforward and effective in the treatment of eyes with an aphakic capsule., Competing Interests: None

Background: Pseudomonas aeruginosa ( P. aeruginosa ) is considered a common pathogenic bacterium. Choroidal metastatic mucinous abscess caused by P. aeruginosa is rarely reported., Case Summary: We describe the diagnostic and treatment processes of a case involving a complex choroidal space-occupying lesion. Our analyses of early clinical manifestations revealed a high possibility of choroidal melanoma, as indicated by the choroidal space-occupying lesion and uveitis. Further magnetic resonance imaging results revealed no positive evidence for the diagnosis of choroidal melanoma. The exact properties of the space-occupying lesion could not be ascertained prior to surgery. However, the lesion was subsequently confirmed as a metastatic abscess by diagnostic vitrectomy. The occupying lesion was found to occupy 75% of the vitreous cavity in the surgery. The entire white viscous tissue was completely removed, and the necrotic retina was cleaned up. After surgery, microbiological culture revealed mucoid P. aeruginosa , which was sensitive to a variety of antibiotics. The bacterial infection grew and disseminated towards the outside of the eye. After the fifth injection, the left eye was successfully retained., Conclusion: This is a peculiar case because a huge, local, space-occupying lesion had formed due to the dissemination of low-toxic mucinous P. aeruginosa in the blood from the lungs to the choroid. After surgical removal, the bacteria were able to re-grow; thus, local infection re-spread following surgery. The patient lost vision, but we managed to retain the full structure of the eyeball and eliminated the focus of infection., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The first application of 3-alkyl-2-vinylindoles in catalytic asymmetric dearomative cycloadditions was established by chiral phosphoric acid (CPA)-catalyzed (2+3) cycloaddition with azoalkenes, leading to the generation of chiral pyrroloindolines bearing two tetrasubstituted stereogenic centers in good yields (61-96%) and excellent stereoselectivities (all >95:5 dr, 86-99% ee). This reaction has realized the first enantioselective dearomative cycloaddition of 3-alkyl-2-vinylindoles, which brings a new reactivity to this class of vinylindoles and will enrich the chemistry of 3-alkyl-2-vinylindoles. In addition, this approach has provided a useful strategy for the construction of enantioenriched pyrroloindoline skeletons bearing two tetrasubstituted stereogenic centers. More importantly, the bioassay of these chiral pyrroloindolines has revealed that some compounds exhibit strong anti-cancer activity against Hela and MCF-7 cell lines, which will be helpful for discovering anti-cancer drug candidates.

Aim: The aim of our study was to clarify the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in spontaneously hypertensive rats (SHR)., Main Methods: Adult male rats were divided into normal blood pressure Wistar-Kyoto rats (WKY) control (WKY-CON), WKY rats with CIHH treatment (WKY-CIHH), SHR control (SHR-CON) and SHR with CIHH treatment (SHR-CIHH) groups. SHR-CIHH and WKY-CIHH rats were subjected to hypobaric hypoxia simulating 4000-m altitude for 35 days, 5 h per day. Arterial blood pressure and cardiac function parameters, including ejection fraction, fractional shortening and left ventricular (LV) wall thickness, were evaluated. Cardiac pathomorphology and myocardial fibrosis were determined. The expression of angiotensin-converting enzyme (ACE), ACE2, Ang II, Ang1-7, AT1 receptor, Mas receptor, IL-6, TNF-α，IL-10, SOD and MDA were assayed in myocardium., Key Findings: CIHH significantly decreased arterial blood pressure, alleviated LV hypertrophy, and improved cardiovascular function in SHR (P < 0.05-0.01). Also, CIHH protected SHR heart against morphological changes and fibrosis. In addition, CIHH significantly down-regulated the ACE/Ang II/AT1 receptor axis and up-regulated the ACE2/Ang1-7/Mas axis of renin-angiotensin system (RAS) in SHR (P < 0.05-0.01). CIHH significantly reduced IL-6, TNF-α, and MDA levels, but increased IL-10 and SOD in SHR myocardium (P < 0.05-0.01)., Significance: The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To investigate the effect and safety of ulnar osteochondroma resection, ulnar minimally invasive osteotomy, external fixation and ulnar lengthening in the treatment of forearm deformity of metaphyseal extension of ulna., Methods: From August 2005 to December 2013, there were 20 cases of ulnar metaphyseal sequelae, including 15 males and 5 females, aged from 7 to 13(10.00±2.34) years, the course of disease ranged for 6 to 11(8.10±1.52) months. The clinical manifestations were shortening of the affected forearm and bending to the ulnar side. The postoperative evaluation included pain, activities of daily living, orthopedic effect and the range of motion of wrist, elbow and forearm. The radiological evaluation included ulnar length, radial joint inclination angle and wrist epiphysis growth., Results: All patients healed without infection. The only operation related to complications was ulnar lengthening, including 1 case of nonunion, 2 cases of ulnar lengthening callus fracture and 1 case of temporary radial nerve palsy. All patients were followed up for 4 to 7.5 years, with an average of (6.03±1.33) years. There were statistically significant differences in changes of wrist radial deviation, ulnar deviation, forearm pronation and supination in all cases ( P <0.05). Radiological evaluation parameters (ulnar variance, radial joint angle, wrist slip) were improved, and the differences were statistically significant( P <0.05). The modified Green and O'Brien wrist function scores at the last follow-up were significantly different from those before operation ( P <0.05). The clinical effect of wrist joint was significantly different from that before operation ( P <0.05). The Mayo elbow function scoreat the latest follow-up was significantly different from that before operation ( P <0.05). The clinical effect of elbow joint was significantly different from that before operation ( P <0.05)., Conclusion: Ulnar lengthening is not beneficial to prevent the development of long-term deformity. Simple resection of osteochondroma of distal ulna is beneficial to prevent the development of deformity. Patients with limited rotation of wrist joint and forearm and strong demand for improvement of appearance can be actively treated.

A novel protocol for the transition metal-free 1,2-addition of polyfluoroaryl boronate esters to aldehydes and ketones is reported, which provides secondary alcohols, tertiary alcohols, and ketones. Control experiments and DFT calculations indicate that both the ortho-F substituents on the polyfluorophenyl boronates and the counterion K + in the carbonate base are critical. The distinguishing features of this procedure include the employment of commercially available starting materials and the broad scope of the reaction with a wide variety of carbonyl compounds giving moderate to excellent yields. Intriguing structural features involving O-H⋅⋅⋅O and O-H⋅⋅⋅N hydrogen bonding, as well as arene-perfluoroarene interactions, in this series of racemic polyfluoroaryl carbinols have also been addressed., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Accumulating evidence demonstrates that the nucleus tractus solitarii (NTS) neurons serve as central respiratory chemoreceptors, but the underlying molecular mechanisms remain undefined. The present study investigated the expression of acid-sensitive ether-à-go-go-gene-like (Elk, Kv12) channels in the NTS of mice. Immunofluorescence staining was used to observe the distribution and cellular localization of the Kv12 channels in NTS neurons. Western blot and quantitative real-time PCR (qPCR) were used to evaluate protein and mRNA expression levels of Kv12 channels. The results showed that all of the three members (Kv12.1, Kv12.2, Kv12.3) of the Kv12 channel family were expressed in NTS neurons, and their expressions were co-localized with paired-like homeobox 2b gene (Phox2b) expression. The expression of Kv12.1 mRNA was the largest, whereas the expression of Kv12.3 was the least in the NTS. The results suggest Kv12 channels are expressed in Phox2b-expressing neurons in the NTS of mice, which provides molecular evidence for pH sensitivity in Phox2b-expressing NTS neurons.

Organoboron compounds have important synthetic value and can be applied in numerous transformations. The development of practical and convenient ways to synthesize boronate esters has thus attracted significant interest. Photoinduced borylations originated from stoichiometric reactions of alkanes and arenes with well-defined metal-boryl complexes. Now, photoredox-initiated borylations, catalyzed by either transition metal or organic photocatalysts, and photochemical borylations with high efficiency have become a burgeoning area of research. In this Focus Review, we summarize research on photoinduced borylations, especially emphasizing recent developments and trends. This includes the photoinduced borylation of arenes, alkanes, aryl/alkyl halides, activated carboxylic acids, amines, alcohols, and so on based on transition metal catalysis, metal-free organocatalysis, and direct photochemical activation. We focus on reaction mechanisms involving single-electron transfer, triplet-energy transfer, and other radical processes.

Objective: To explore the effect of subpressure on the bonding strength of resin to polycrystalline particulates modified zirconia ceramic. Methods: One hundred and twenty pre-sintered zirconia discs were prepared and divided into the control group, the sandblasting group and the 30, 50, 70 s acid etching group (24 per group) by the random number table method. There was no additional treatment in the control group and sandblasting group before sinering. The 30, 50, and 70 s acid etching groups were immersed in HF for 30, 50, 70 s, respectively, and then they were placed into CaCl 2 solution for 90 s and dipped in NaOH solution at 80 ℃ for 2 h. After sintering, the sandblasting group was subjected to sandblasting. The surface tomography and roughness were tested. According to whether subpressure was applied or not after the adhesives were applied, each group was randomly divided into two subgroups with a random number table: a subpressure subgroup and a normal pressure subgroup (12 per subgroup). Resin columns were bonded to these specimens. Shear bonding strength (SBS) test was conducted and the bonding interface, fracture surface and failure mode were analyzed. Results: The surface of control group was smooth, and its roughness was (0.24±0.11) μm. The rough surface was formed after sandblasting in the sandblasting group, and its roughness was (0.95±0.12) μm. The surface roughness of 30, 50, 70 s acid etching groups [(0.60±0.15), (1.04±0.11), (1.57±0.16) μm] increased as the HF immersion time prolonged, and the difference in surface roughness of zirconia specimens among each group was statistically significant ( P <0.05). The SBS values between zirconia and resin of all the subpressure subgroups, namely: the control group, the sandblasting group, and the 30, 50, 70 s acid etching group [(13.56±1.19), (20.98±2.11), (17.37±2.44), (24.19±2.97), (21.36±2.16) MPa] were significantly stronger than those in the normal pressure subgroups, namely: the control group, sandblasting group, 30, 50, 70 s acid etching group [(10.74±0.93), (18.47±2.14), (14.81±1.54), (20.74±2.56), (17.75±2.54) MPa] ( P <0.05). No obvious gaps and bubbles were observed in the bonding interfaces in subpressure subgroups. The proportion of mixed failure was significantly increased after applying subpressure ( P <0.05). Conclusions: The subpressure can effectively enhance the bonding strength between the resin and polycrystalline particulates modified zirconia ceramic and improve the bonding effect.

Purpose: To assess the impact of comorbidity on treatment outcomes in patients with locally recurrent nasopharyngeal carcinoma (lrNPC) using intensity-modulated radiotherapy (IMRT) and to develop a nomogram that combines prognostic factors to predict clinical outcome and guide individual treatment., Methods: This was a retrospective analysis of patients with lrNPC who were reirradiated with IMRT between 2003 and 2014. Comorbidity was evaluated by Adult Comorbidity Evaluation-27 grading (ACE-27). The significant prognostic factors (P < 0.05) by multivariate analysis using the Cox regression model were adopted into the nomogram model. Harrell concordance index (C-index) calibration curves were applied to assess this model., Results: Between 2003 and 2014, 469 lrNPC patients treated in our institution were enrolled. Significant comorbidity (moderate or severe grade) was present in 17.1% of patients by ACE-27. Patients with no or mild comorbidity had a 5-year overall survival (OS) rate of 36.2 versus 20.0% among those with comorbidity of moderate or severe grade (P < 0.0001). The chemotherapy used was not significantly different in patients with lrNPC (P > 0.05). For the rT3-4 patients, the 5-year OS rate in the chemotherapy + radiation therapy (RT) group was 30.0 versus 16.7% for RT only (P = 0.005). The rT3-4 patients with no or mild comorbidity were associated with a higher 5-year OS rate in the chemotherapy + RT group than in the RT only group (32.1 and 17.1%, respectively; P=0.003). However, for the rT3-4 patients with a comorbidity (moderate or severe grade), the 5-year OS rate in the chemotherapy + RT group vs. RT alone was not significantly different (15.7 vs. 15.0%, respectively; p > 0.05). Eight independent prognostic factors identified from multivariable analysis were fitted into a nomogram, including comorbidity. The C-index of the nomogram was 0.715. The area under curves (AUCs) for the prediction of 1-, 3-, and 5-year overall survival were 0.770, 0.764, and 0.780, respectively., Conclusion: Comorbidity is among eight important prognostic factors for patients undergoing reirradiation. We developed a nomogram for lrNPC patients to predict the probability of death after reirradiation and guide individualized management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Sun, Wang, Tian, Peng, Wang, Xiao, Chen, Deng and Han.)

We report herein a mild procedure for the copper-catalyzed oxidative cross-coupling of electron-deficient polyfluorophenylboronate esters with terminal alkynes. This method displays good functional group tolerance and broad substrate scope, generating cross-coupled alkynyl(fluoro)arene products in moderate to excellent yields. Thus, it represents a simple alternative to the conventional Sonogashira reaction., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

Background: Lipid abnormalities are prevalent among people living with human immunodeficiency virus (HIV) (PLWH) and contribute to increasing risk of cardiovascular events. This study aims to investigate the incidence of dyslipidemia and its risk factors in PLWH after receiving different first-line free antiretroviral regimens., Methods: PLWH who sought care at the Third People's Hospital of Shenzhen from January 2014 to December 2018 were included, and the baseline characteristics and clinical data during the follow-up were collected, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The risk factors of dyslipidemia after antiretroviral therapy were analyzed with the generalized estimating equation model., Results: Among the 7623 PLWH included, the mean levels of TC, HDL-C and LDL-C were 4.23 ± 0.85 mmol/L, 1.27 ± 0.29 mmol/L and 2.54 ± 0.65 mmol/L, respectively, and the median TG was 1.17 (IQR: 0.85-1.68) mmol/L. Compared with that in PLWH receiving tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) + ritonavir-boosted lopinavir (LPV/r), zidovudine (AZT) + 3TC + efavirenz (EFV), and AZT + 3TC + LPV/r, the incidence of dyslipidemia was lower in PLWH receiving TDF + 3TC + EFV. In multivariate analysis, we found that the risks of elevations of TG, TC, and LDL-C were higher with TDF + 3TC + LPV/r (TG: odds ratio [OR] = 2.82, 95% confidence interval [CI]: 2.55-3.11, P < 0.001; TC: OR = 1.24, 95% CI: 1.14-1.35, P < 0.001; LDL: OR = 1.06, 95% CI: 1.00-1.12, P = 0.041), AZT + 3TC + EFV (TG: OR = 1.41, 95% CI: 1.28-1.55, P < 0.001; TC: OR = 1.43, 95% CI: 1.31-1.56, P < 0.001; LDL: OR = 1.18, 95% CI: 1.12-1.25, P < 0.001), and AZT + 3TC + LPV/r (TG: OR = 3.08, 95% CI: 2.65-3.59, P < 0.001; TC: OR = 2.40, 95% CI: 1.96-2.94, P < 0.001; LDL: OR = 1.52, 95% CI: 1.37-1.69, P < 0.001) than with TDF + 3TC + EFV, while treatment with TDF + 3TC + LPV/r was less likely to restore HDL-C levels compared with TDF + 3TC + EFV (OR = 0.95, 95% CI: 0.92-0.97, P < 0.001). In addition to antiretroviral regimens, antiretroviral therapy duration, older age, overweight, obesity and other traditional factors were also important risk factors for dyslipidemia., Conclusion: The incidence of dyslipidemia varies with different antiretroviral regimens, with TDF + 3TC + EFV having lower risk for dyslipidemia than the other first-line free antiretroviral regimens in China.

A highly selective and general photoinduced C-Cl borylation protocol that employs [Ni(IMes) 2 ] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the radical borylation of chloroarenes is reported. This photoinduced system operates with visible light (400 nm) and achieves borylation of a wide range of chloroarenes with B 2 pin 2 at room temperature in excellent yields and with high selectivity, thereby demonstrating its broad utility and functional group tolerance. Mechanistic investigations suggest that the borylation reactions proceed via a radical process. EPR studies demonstrate that [Ni(IMes) 2 ] undergoes very fast chlorine atom abstraction from aryl chlorides to give [Ni I (IMes) 2 Cl] and aryl radicals. Control experiments indicate that light promotes the reaction of [Ni I (IMes) 2 Cl] with aryl chlorides generating additional aryl radicals and [Ni II (IMes) 2 Cl 2 ]. The aryl radicals react with an anionic sp 2 -sp 3 diborane [B 2 pin 2 (OMe)] - formed from B 2 pin 2 and KOMe to yield the corresponding borylation product and the [Bpin(OMe)] •- radical anion, which reduces [Ni II (IMes) 2 Cl 2 ] under irradiation to regenerate [Ni I (IMes) 2 Cl] and [Ni(IMes) 2 ] for the next catalytic cycle.

Objective: To explore the accuracy of occlusal contacts on digital model made by intraoral scanner. Methods: Twenty healthy subjects [6 males, 14 females, (24.4±1.4) years old] with intact dentition were randomly recruited from postgraduate students in Capital Medical University School of Stomatology who volunteered to participate in this study. For each participant, the 2nd and 3rd quadrant of natural dentition was scanned. A diagnostic test design was performed. The occlusal contacts of the maximal intercuspal position (MIP) were extracted with the transillumination of silicone interocclusal records, and the extraction threshold was set as ≤50 μm. Intraoral scanning system was used to scan in MIP and generate occlusal contacts on digital model. Five groups were designed as test groups according to included tooth position: group 1 (buccal scanning ranged from tooth 21 to 23), group 2 (buccal scanning ranged from tooth 23 to 26), group 3 (buccal scanning ranged from tooth 24 to 26), group 4 (buccal scanning ranged from tooth 25 to 26), group 5 (buccal scanning ranged from tooth 21 to 26). Five groups occlusal contacts on digital model were generated respectively. According to the relevant literature, the upper occlusal surface was divided into 28 partitions, and the accuracy of occlusal contacts on digital model was calculated with the transillumination of silicone interocclusal records as the reference standard. Subgroup analysis was performed according to anterior teeth area, premolars area and molars area. Results: The accuracy of occlusal contacts on digital models of the half dentition in five buccal scanning positions were: group 1 (86.8%), group 2 (92.0%), group 3 (90.7%), group 4 (91.1%), group 5 (90.4%), and the accuracy of occlusal contacts in group 1 was significantly lower than those in the other four groups ( P <0.05). The accuracy of anterior teeth area were 85.6%-93.9%; the accuracy of premolar area were 92.5%-94.4%; the accuracy of molar area were 77.3%-93.6%, group 1 was significantly lower than those in the group 4 in molars area ( P <0.05), the accuracy of anterior area was statistically less than premolars area and molars area in group 1 ( P <0.05). There was no statistical difference in pairwise comparison between the three sections ( P >0.05). Conclusions: The digital models scanned intraoral methods provide accurate, quantitative measures of occlusal contacts when transillumination contacts are the reference standard.

In this paper, a label-free fluorescence nanoprobe is constructed based on poly(thymine) single strand DNA-templated Copper nanocluster (denote as: T-CuNCs) for the detection of hydrogen peroxide. In the assay, the fluorescent T-CuNCs will generate though the reaction of Cu 2+ , poly(thymine) and sodium ascorbate. However, the hydroxyl radical ( . OH) will generated in the presence of H 2 O 2 , which is able to induced the oxidative lesions of poly(thymine) single chain DNA and lead to the poly(thymine) being splitted into shorter or single oligonucleotide fragments and lose the ability to template the fluorescent T-CuNCs again. Therefore, H 2 O 2 can be detected by monitoring the fluorescence strength change of T-CuNCs. The experimental results show that the fluorescence intensity change of T-CuNCs has fantastic linearity versus H 2 O 2 concentration in the range of 1-30 μM (R 2  = 0.9947) and 30-80 μM (R 2  = 0.9972) with the limit of detection (LOD) as low as 0.5 μM (S/N = 3). More important, the fluorescent nanoprobe was also successfully utilized on the detection of H 2 O 2 in serum samples. Therefore, a label-free, costless and effective fluorescence method has been established for the detection of H 2 O 2 , the intrinsic properties of the nanoprobe endow its more potential applications in chemical and biological study., Competing Interests: Declaration of competing interest None of the authors have any competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Compressed materials of fossil foliage described here as Itea polyneura sp. nov. (Iteaceae) were collected from the Oligocene of Wenshan, Yunnan Province, southwestern China. The identification is based on the following characters: eucamptodromous secondary veins, strict scalariform tertiary veins, irregular tooth with setaceous apex. The leaf morphology of all modern and fossil species was compared with the new species from Wenshan and show that I. polyneura is most similar to the extant East Asian species Itea omeiensis , which inhabits subtropical forests of southern China. This discovery represents the first unambiguous leaf fossil record of Itea in East Asia. Together with other species in the Wenshan flora and evidence from several other flora in southern China, these findings demonstrate that Itea from East Asia arose with the Paleogene modernization., Competing Interests: There is no possibility of a potential conflict of interest., (© 2020 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Gastric cancer is a disease with high mortality, which threatens the health of people for a long time. At present, the main treatment methods are surgery and chemotherapy, but these methods have great harm to the human body. However, it is found that the active ingredients of traditional Chinese medicine have an obvious therapeutic effect in the adjuvant treatment of the tumor. Therefore, the active ingredients of traditional Chinese medicine have become a research hotspot in the anti-tumor field. In recent years, many related researchers have been particularly active in studying the in vitro activity and mechanism of active ingredients of traditional Chinese medicine on human gastric cancer cells. In this paper, the Chinese herbal medicine extracts, polysaccharides, alkaloids, saponins, flavones, terpenes, quinones, volatile oils, esters, phenols, protein components and other active ingredients of Chinese medicine were used as the starting points to investigate the anti-gastric cancer mechanism, such as inhibiting cell proliferation and inducing apoptosis of cancer cells, inhibiting cell invasion and migration; inhibiting over-expression of vascular endothelial growth factor(VEGF); interfering with cell mitosis; and regulating cell signaling pathways. Their in vitro inhibitory activity and mechanism for gastric cancer cells were described in this study, providing a theoretical reference for the development and application of anti-gastric cancer drugs.