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Shi-Hua Yan,1,2 Yong Chen,3 Zhi-Qian Huang,1 Wen-Xi Zhong,1 Xiao-Tian Wang,1 Yang-Can Tang,1 Xu-Yi Zhao,1 Yu-Shan Wu,1 Chun Zhou,4 Wei Zhu,5 Wei Xiao,1,6 Xuan Li,2 Dong-Shu Zhang1,2 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department of Traditional Chinese Medicine, The Tenth affiliated Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, 523058, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4School of Pharmaceutical Sciences; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, People’s Republic of China; 6Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of ChinaCorrespondence: Dong-Shu Zhang, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Email nyzds@sina.com Wei Xiao, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China, Email xw7688@smu.edu.cnPurpose: Acupoint autohemotherapy (A-AHT) has been proposed as an alternative and complementary treatment for atopic dermatitis (AD), yet the exact role of its blood component in terms of therapeutic efficacy and mechanism of action is still largely unknown.Methods: This study aimed to evaluate the therapeutic efficacies and action mechanisms of intramuscular injections of autologous whole blood (AWB) and mouse immunoglobulin G (IgG) (autologous or heterologous) at acupoints on 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse models. Serum levels of total immunoglobulin E (IgE), IgG, interleukin-10 (IL-10), and interferon-gamma (IFN-γ) were measured, as well as mRNA expression levels of Forkhead box P3 (FoxP3), IL-10 and IFN-γ in dorsal skin lesions, and IL-10+, IFN-γ+ and FoxP3+CD4+T cells in murine spleen.Results: It showed that repeated acupoint injection of AWB, autologous total IgG (purified from autologous blood in AD mice) or heterologous total IgG (purified from healthy blood in normal mice) effectively reduced the severity of AD symptoms and decreased epidermal and dermal thickness as well as mast cells in skin lesions. Additionally, AWB acupoint injection was found to upregulate FoxP3+, IL-10+ and IFN-γ+ CD4+T cells in murine spleen, suppressing the production of IgE antibodies and increasing that of IgG antibodies in the serum. Furthermore, both AWB and autologous total IgG administrations significantly elevated FoxP3 expression, mRNA levels of IL-10 and IFN-γ in dorsal skin lesions. However, acupoint injection of heterologous total IgG had no effect on regulatory T (Treg) and Th1 cells modulation.Conclusion: These findings suggest that the therapeutic effects of A-AHT on AD are mediated by IgG-induced activation of Treg cells.Keywords: autologous whole blood, acupoint injection, atopic dermatitis, anti-idiotypic immunomodulation, Tregs

Hao Zhang,1 Chen Liang,2 Xinxin Hou,3 Ling Wang,1 Dongsheng Zhang41Department of Imaging and Nuclear Medicine, Medical School of Southeast University, Nanjing, Jiangsu, 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 3Department of Pathology, Medical School of Henan Polytechnic University, Jiaozuo, Henan, 4Jiangsu Key Laboratory for Biomaterials and Devices, Medical School, Southeast University, Nanjing, People’s Republic of ChinaAbstract: Combination therapy for lung cancer has garnered widespread attention. Radiation therapy, gene therapy, and molecular targeted therapy for lung cancer have certain effects, but the disadvantages of these treatment methods are evident. Combining these methods can decrease their side effects and increase their curative effects. In this study, we constructed a pYr-ads-8-5HRE-cfosp-iNOS-IFNG plasmid (a gene circuit that can express IFNγ), which is a gene circuit, and used that plasmid together with C225 (cetuximab) to prepare gene-loaded immunomagnetic albumin nanospheres (IMANS). Moreover, we investigated the therapeutic effects of gene-loaded IMANS in combination with radiation therapy on human lung cancer in vitro and in vivo. The results showed that this gene circuit was successively constructed and confirmed that the expression of INFγ was increased due to the gene circuit. Gene-loaded IMANS combined with radiation therapy demonstrated improved results in vitro and in vivo. In conclusion, gene-loaded IMANS enhanced the efficacy of combination therapy, solved problems related to gene transfer, and specifically targeted lung cancer cells.Keywords: gene circuit, combination therapy, magnetic albumin nanospheres

Hao Zhang,1 Xinxin Hou,2 Mei Lin,3 Ling Wang,1 Hongbo Li,4 Chenyan Yuan,1 Chen Liang,1 Jia Zhang,5 Dongsheng Zhang1,6 1Medical School of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Medical School of Henan Polytechnic University, Jiaozuo, Henan, People’s Republic of China; 3Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, People’s Republic of China; 4Department of Ultrasound in Medicine, The First Affiliated Hospital (Jiangsu Province Hospital of TCM), Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Jiangsu Cancer Hospital, Nanjing, Jiangsu, People’s Republic of China; 6Jiangsu Key Laboratory For Biomaterials and Devices, Nanjing, Jiangsu, People’s Republic of China Abstract: As one of the most common malignant tumors, the clinical and socio-economic consequences of lung cancer are significant. Currently, surgery is the main treatment strategy for this disease, but the survival rates of lung cancer patients are not ideal due to the high recurrence rate of the disease. Therefore, many researchers are exploring new specific therapeutic methods that are highly curative and minimally cytotoxic to healthy tissues. To this end, albumin nanospheres simultaneously were loaded with super-paramagnetic iron oxide nanoparticles (as gene vector and anticancer gene), and plasmid pDONR223-IFNG, and modified with anti-EGFR monoclonal antibody cetuximab as therapy. Targeting agents, namely gene-loaded immunomagnetic albumin nanospheres (cetuximab [C225]-IFNG-IMANS), were prepared for targeted lung carcinoma cells (GLC-82 cell lines). Transmission electron microscopy images showed that the C225-IFNG-IMANS were successfully prepared, and the ability of the nanospheres to target GLC-82 cells in vitro was confirmed by Prussian blue staining, immunofluorescence experiments, and magnetic resonance imaging. Transfection photographs and agarose gel electrophoresis proved that pDONR223-IFNG could be encased in the albumin nanospheres. A Cell Counting Kit-8 assay showed that the combination therapy group had significantly more therapeutic effects on GLC-82 cells than other therapy groups. A flow cytometry assay showed that the apoptotic index of the combined treatment group was 67.68%, whereas the indices of the C225 group, gene therapy group, and magnetic fluid hyperthermia group were 12.2%, 16.34%, and 20.04% respectively. Therefore, the combination of thermal treatment, molecular targeted treatment, and gene treatment synergistically targets GLC-82 cells, and the use of C225-IFNG-IMANS as a gene or drug carrier offers a novel and promising approach for the treatment of lung cancer. Keywords: targeting gene therapy, nano-drug, magnetic nanoparticles

Yijie Chen,1,2,* Xinran Wang,3,4,* Ting Liu,3,4 Ding Sheng-zi Zhang,1,2 Yunfei Wang,3,4 Hongchen Gu,1,2 Wen Di3,4 1State Key Laboratory of Oncogenes and Related Genes, Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, 2School of Biomedical Engineering and Med-X Research Institute, 3Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 4Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Therapeutic antiangiogenesis strategies have demonstrated significant antitumor efficacy in ovarian cancer. Recently, RNA interference (RNAi) has come to be regarded as a promising technology for treatment of disease, especially cancer. In this study, vascular endothelial growth factor (VEGF)-small interfering RNA (siRNA) was encapsulated into a magnetic mesoporous silica nanoparticle (M-MSN)-based, polyethylenimine (PEI)-capped, polyethylene glycol (PEG)-grafted, fusogenic peptide (KALA)-functionalized siRNA delivery system, termed M-MSN_VEGF siRNA@PEI-PEG-KALA, which showed significant effectiveness with regard to VEGF gene silencing in vitro and in vivo. The prepared siRNA delivery system readily exhibited cellular internalization and ease of endosomal escape, resulting in excellent RNAi efficacy without associated cytotoxicity in SKOV3 cells. In in vivo experiments, notable retardation of tumor growth was observed in orthotopic ovarian tumor-bearing mice, which was attributed to significant inhibition of angiogenesis by systemic administration of this nanocarrier. No obvious toxic drug responses were detected in major organs. Further, the magnetic core of M-MSN_VEGF siRNA@PEI-PEG-KALA proved capable of probing the site and size of the ovarian cancer in mice on magnetic resonance imaging. Collectively, the results demonstrate that an M-MSN-based delivery system has potential to serve as a carrier of siRNA therapeutics in ovarian cancer. Keywords: antiangiogenesis, small interfering RNA, mesoporous silica nanoparticles, vascular endothelial growth factor, ovarian cancer

Yan-li An, Fang Nie, Zi-yu Wang, Dong-sheng ZhangJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of ChinaAim: Our objective was to prepare a new nano-sized realgar particle and characterize its antitumor effect on tumor cells.Methods: Nanoparticles were prepared by coprecipitation and were detected by transmission electron microscopy, scanning electron microscopy, energy dispersive spectrometry (EDS), and dynamic light scattering. An anti-proliferative effect of realgar nanoparticles on rat glioma (C6) cells was determined by the MTT assay. Cell cycle and apoptosis rates were observed by flow cytometry. Apoptosis-related gene expression was detected by immunofluorescence staining.Results: Realgar nanoparticles were successfully prepared. The particles were spherical, with an average diameter of approximately 80 nm, and contained arsenic and sulfur elements. Realgar nanoparticles inhibited C6 cell proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment of C6 cells with realgar nanoparticles significantly increased the proportions of cells in S and G2/M phases, decreased the proportion of cells in G0/G1 phase, downregulated Bcl-2 expression, and substantially upregulated Bax expression.Conclusion: Realgar nanoparticles significantly inhibited C6 glioma cell proliferation and promoted cell apoptosis by inducing the upregulation of Bax and downregulation of Bcl-2 expression. Realgar nanoparticles are a promising in vitro anti-cancer strategy and may be applicable for human cancer therapy studies.Keywords: realgar, preparation, characterization, inhibitory effect

Because of the huge size of the common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) genome of 17,300 Mb, sequencing and mapping of the expressed portion is a logical first step for gene discovery. Here we report mapping of 7104 expressed sequence tag (EST) unigenes by Southern hybridization into a chromosome bin map using a set of wheat aneuploids and deletion stocks. Each EST detected a mean of 4.8 restriction fragments and 2.8 loci. More loci were mapped in the B genome (5774) than in the A (5173) or D (5146) genomes. The EST density was significantly higher for the D genome than for the A or B. In general, EST density increased relative to the physical distance from the centromere. The majority of EST-dense regions are in the distal parts of chromosomes. Most of the agronomically important genes are located in EST-dense regions. The chromosome bin map of ESTs is a unique resource for SNP analysis, comparative mapping, structural and functional analysis, and polyploid evolution, as well as providing a framework for constructing a sequence-ready, BAC-contig map of the wheat genome.

The labial groove-textures of upper central incisors were defined and explored to imitate the elaborate groove-textures for aesthetic restorations. In the current study, 158 upper central incisors were selected from 79 volunteers aged from 19 to 24 and recruited from Sichuan University in Chengdu of China. The length, width, depth, combination and distribution of the horizontal and vertical grooves on the labial surface were investigated by an optical measurement method, based on the Shadow Moiré technology and Temporal Fourier analysis. Vertical grooves were confirmed to be present in 94% of the samples and horizontal grooves in 77%. Perfect symmetry was shown in the vertical grooves of the same tooth, as well as in the homonymous teeth. The majority of horizontal grooves were distributed in the proximity of the cervical fourth and the middle of the crown. Based on the combination and distribution of the grooves, eight basic labial groove-texture types of maxillary central incisors were classified. The subtle morphological characters of natural teeth could be recorded by the new method, and it could also provide the minute groove-texture for dentists and technicians to achieve an aesthetic appearance for a restoration. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection in diffuse large B-cell lymphoma (DLBCL) patients is a common complication in China. However, the clinical relevance of HBV infection with respect to DLBCL disease stages and patient survival remains unclear. The main objective of the current study was to analyze the clinical features and to evaluate the prognostic factors of HBV infection in DLBCL patients.Methods: In this retrospective study, DLBCL patients were divided into two groups as HBsAg-positive (n = 81) and HBsAg-negative (n = 181) patients. The HBsAg-positive patients were further divided into two subgroups based on their hepatic function during chemotherapy. Various statistical analyses were used to determine the significance of the relevant clinical parameters.Results: Compared with the HBsAg-negative group, the HBsAg-positive DLBCL group displayed a younger median onset age (46 year vs 51), more advanced stage at grade III/IV (58% vs 42%, p = 0.016), and more frequent hepatic dysfunction before (21% vs 5.5%, p < 0.001) and during (49.4% vs 16.6%, p < 0.001) chemotherapy. Female DLBCL patients exhibited a higher frequency of HBsAg positivity (p = 0.006). However, in both groups the median overall survival (OS) duration (55.8 vs 66.8 months) and response rates (91% vs 90.4%) were similar. In the HBsAg-positive DLBCL group, the poor prognostic factors were advanced stage (p < 0.001) and hepatic dysfunction during chemotherapy (p = 0.02). The OS of HBsAg-positive patients with hepatic dysfunction during chemotherapy was significantly shorter than those without liver dysfunction (p = 0.016), and the OS rates at 3 years were 48% and 72%, respectively. The use of rituximab did not increase the rates of liver dysfunction in HBsAg-positive DLBCL patients.Conclusion: Compared with HBsAg-negative patients, the HBsAg-positive DLBCL patients had earlier onset and more advanced stage. The disease stage and hepatic dysfunction during chemotherapy and were two significant prognostic factors in the HBsAg-positive DLBCL patients. This study suggests that prophylactic treatment of HBV may be of great importance in the cases of HBsAg-positive patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: For severe burn victims suffering from total loss of upper and lower eyelids, skin graft or skin flap is normally used to cover the lesion and to protect the cornea, preventing corneal ulcer and simultaneously preparing for corneal transplantation. However, a new problem arises after the formation of the new palpebral fissure, that is, the reconstructed eyelids cannot open and close like the normal eyelids and the eyeball movement is limited, which exposes the cornea to dry air resulting in ulceration. In this article, we present a simple technique to partially solve this problem. METHODS: Five burn victims who lost their eyelids received treatment: stumps of upper and lower eyelids bulbar conjunctiva were dissected and pulled together as the lining of the conjunctival sac. Intermediate split-thickness skin was then immediately grafted as the new eyelids' skin. After 3 months, a 2-cm transverse incision was made 5mm below the normal palpebral fissure to open the conjunctival sac and new 'eyelids' were formed. RESULTS: The patients were followed for 2-9 years. No lagophthalmos and xerophthalmia were found. When the patients raised their heads in the supine position, they could see outside. When they bowed their heads, the cornea was protected. Their remaining vision was rescued and an average 0.4 vision recovered. Most of the patients went back to work. CONCLUSION: The opening and closing function of the eyelids can partially be replaced by movements of the head and neck using this technique. It seems to be a reliable option to rescue the vision in these types of challenging situations. [ABSTRACT FROM AUTHOR]

Carbon emission reduction is an important measure to mitigate the greenhouse effect, which has become a hotspot in global climate change research. To contribute to this, here, we fabricated two Co-based metal-organic frameworks (Co-MOFs), namely, {[Co 3 (NTB) 2 (bib)]·(DMA) 2 ·(H 2 O) 4 } n (DZU-211) and {[Co 3 (NTB) 2 (bmip)]·(DMA) 2 } n (DZU-212) (H 3 NTB = 4,4',4″-nitrilotribenzoic acid, bib = 1,4-bis(imidazol-1-yl)-butane, bmip = 1,3-bis(2-methyl-1 H -imidazol-1-yl)propane) to realize efficient CO 2 /N 2 separation by dividing coordination spaces into suitable pores with narrow windows. DZU-211 reveals a 3D open porous framework, while DZU-212 exhibits a 3D double-fold interpenetrated structure. The two MOFs both possess large coordination spaces and small open pore sizes, via the bib ligand insertion and framework interpenetration, respectively. Comparatively, DZU-211 reveals superior selective CO 2 uptake properties due to its more suitable pore characteristics. Gas sorption experiments show that DZU-211 has a CO 2 uptake of 52.6 cm 3 g -1 with a high simulated CO 2 /N 2 selectivity of 101.7 (298 K, 1 atm) and a moderate initial adsorption heat of 38.1 kJ mol -1 . Moreover, dynamic breakthrough experiments confirm the potential application of DZU-211 as a CO 2 separation material from postcombustion flue gases.

Background: APG-1387 is a novel second mitochondrial-derived activator of caspases mimetic, small-molecule inhibitor targeting inhibitor of apoptosis proteins. We report results from two phase I trials evaluating the tolerability, safety, and antitumor activity of APG-1387 monotherapy and APG-1387 plus toripalimab [a programmed cell death 1 (PD-1) inhibitor] for advanced solid tumors., Patients and Methods: Participants aged ≥18 years who had histologically confirmed advanced solid tumors with no appropriate standard of care (or refractory to standard care) were eligible. Patients received escalating intravenous doses of APG-1387 alone or combined with fixed-dose toripalimab (240 mg every 3 weeks) in a '3 + 3' design. Primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) in the monotherapy trial, and recommended phase II dose (RP2D) in the combination therapy trial. Secondary endpoints included the pharmacokinetic and pharmacodynamic profiles and preliminary efficacy in both trials., Results: In the monotherapy trial, 28 subjects were enrolled and received ≥1 treatment cycle. No DLT was reported among the 28 subjects, and the MTD was not reached. One participant (3.6%) had a grade ≥3 treatment-related adverse event (TRAE) of alanine aminotransferase elevation. In efficacy analysis of 23 participants, none achieved an objective response, and the disease control rate was 21.7%. In the combination trial, 22 subjects were enrolled and included in all analyses. There was one DLT of grade 3 lipase elevation. The MTD was not reached. Four grade ≥3 TRAEs occurred in three participants (13.6%), with the most common being lipase elevation (n = 2). The RP2D was 45 mg weekly. The objective response rate was 13.6%, with complete response achieved in one subject, and the disease control rate was 54.5%., Conclusions: APG-1387 45 mg weekly plus toripalimab was well tolerated and is recommended for further study, with preliminary clinical activity observed in study participants with advanced solid tumors., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been introduced for the mobilization of peripheral blood stem cells (PBSCs). However, no cases of acute lung injury (ALI) in healthy donors have been reported, and the underlying mechanisms remain poorly understood. We first reported a case of ALI caused by PEG-rhG-CSF in a healthy Chinese donor, characterized by hemoptysis, hypoxemia, and patchy shadows. Ultimately, hormone administration, planned PBSC collection, leukocyte debridement, and planned PBSC collection resulted in active control of the donor's ALI. The donor's symptoms improved without any adverse effects, and the PBSC collection proceeded without incident. Over time, the lung lesion was gradually absorbed and eventually returned to normal. PEG-rhG-CSF may contribute to ALI in healthy donors via mechanisms involving neutrophil aggregation, adhesion, and the release of inflammatory mediators in the lung. This case report examines the clinical manifestations, treatment, and mechanism of lung injury induced by PEG-rhG-CSF-mobilized PBSCs., (© 2024. Japanese Society of Hematology.)

On-chip integrated metasurface driven by in-plane guided waves is of great interests in various light-field manipulation applications such as colorful augmented reality and holographic display. However, it remains a challenge to design colorful multichannel holography by a single on-chip metasurface. Here we present metasurfaces integrated on top of a guided-wave photonic slab that achieves multi-channel colorful holographic light display. An end-to-end scheme is used to inverse design the metasurface for projecting off-chip preset multiple patterns. Particular examples are presented for customized patterns that were encoded into the metasurface with a single-cell meta-atom, working simultaneously at RGB color channels and for several different diffractive distances, with polarization dependence. Holographic images are generated at 18 independent channels with such a single-cell metasurface. The proposed design scheme is easy to implement, and the resulting device is viable for fabrication, promising plenty of applications in nanophotonics.

Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Despite being an important determinant of health outcomes, measures of structural racism are lacking in studies examining the relationship between the social determinants of health (SDOH) and overdose deaths. The aim of this study is to examine the association between per capita revenue generated from fines and forfeitures, a novel measure of structural racism, and other SDOH with county-level overdose deaths from 2017-2020., Methods: This longitudinal analysis of 2,846 counties from 2017-2020 used bivariate and multivariate Generalized Estimating Equations models to estimate associations between county overdose mortality rates and SDOH characteristics, including the fines and forfeitures measure., Results: In our multivariate model, higher per capita fine and forfeiture revenue (5.76; CI: 4.76, 6.78), households receiving food stamps (1.15; CI: 0.77, 1.53), residents that are veterans (1.07; CI: 0.52, 1.63), substance use treatment availability (4.69; CI: 3.03, 6.33) and lower population density (-0.002; CI: -0.004, -0.001) and percent of Black residents (-0.7`; CI: -1.01, -0.42) were significantly associated with higher overdose death rates. There was a significant additive interaction between the fines and forfeitures measure (0.10; CI: 0.03, 0.17) and the percent of Black residents., Conclusions: Our findings suggest that structural racism, along with other SDOH, is associated with overdose deaths. Future research should focus on connecting individual-level data on fines and forfeitures to overdose deaths and other health outcomes, include measures of justice-related fines, such as court fees, and assess whether interventions aimed at increasing economic vitality in disadvantaged communities impact overdose deaths in a meaningful way., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lindenfeld et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients., (© 2024. The Author(s).)

Astrocytes transfer extracellular functional mitochondria into neurons to rescue injured neurons after a stroke. However, there are no reports on drugs that interfere with intercellular mitochondrial transfer. Chrysophanol (CHR) was an effective drug for the treatment of cerebral ischemia-reperfusion injury (CIRI) and was selected as the test drug. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model and the middle cerebral artery occlusion animal model were established to investigate the effect of CHR on CIRI. The result showed that astrocytes could act as mitochondrial donors to ameliorate neuronal injury. Additionally, the neuroprotective effect of astrocytes was enhanced by CHR, the CHR improved the neuronal mitochondrial function, decreased the neurological deficit score and infarction volume, recovered cell morphology in ischemic penumbra. The mitochondrial fluorescence probe labeling technique has shown that the protective effect of CHR is associated with accelerated astrocytic mitochondrial transfer to neurons. The intercellular mitochondrial transfer may be an important way to ameliorate ischemic brain injury and be used as a key target for drug treatment., 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 Elsevier Inc. All rights reserved.)

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC., (© 2024. The Author(s).)

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8 + T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Aim: Circular RNAs (circRNAs) have been found to be involved in tumor progression, but their role in colorectal cancer (CRC) immune escape remains to be elucidated. Methods: circRNAs differentially expressed in responsive and resistant CRC tissues to programmed cell death 1 (PD-1) antibody therapy were identified by microarray analysis. The clinical and pathological significance of circNCOA3 was validated in a separate cohort of CRC samples. The function of circNCOA3 was explored experimentally. RNA immunoprecipitation and luciferase activity assays were conducted to identify downstream targets of circNCOA3. Results: The circNCOA3 was markedly overexpressed in CRC samples resistant to PD-1 blockade. circNCOA3 expression was significantly correlated with adverse tumor phenotypes and poor outcomes in CRC patients. Knockdown of circNCOA3 expression markedly suppressed the proliferative and invasive capability of CRC cells. Moreover, knockdown of circNCOA3 increased the proportion of CD8 + T cells while decreasing the proportion of myeloid-derived suppressor cells (MDSCs). Knockdown of circNCOA3 inhibited tumor growth and increased the sensitivity to PD-1 antibody treatment in mouse tumor models. Further studies revealed that circNCOA3 acted as a competing endogenous RNA (ceRNA) for miR-203a-3p.1 to influence the level of CXCL1. Conclusion: Our findings indicate that circNCOA3 might be useful as a potential biomarker to predict the efficacy and prognosis of CRC patients treated with anti-PD-1 therapy., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

Photoredox catalytic processes offer the potential for precise chemical reactions using light and materials. The central determinant is identified as interfacial charge transfer, which simultaneously engenders distinctive behavior in the overall reaction. An in-depth elucidation of the main mechanism and highlighting of the complexity of interfacial charge transfer can occur through both diffusive and direct transfer models, revealing its potential for sophisticated design in complex transformations. The fundamental photophysics uncover these comprehensive applications and offer a clue for future development. This research contributes to the growing body of knowledge on interfacial charge transfer in photoredox catalysis and sets the stage for further exploration of this fascinating area of research., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: During the current period of the pandemic, telehealth has been a boon to the healthcare system by providing quality healthcare services at a safe social distance. However, there has been slow progress in telehealth services in low- and middle-income countries with little to no evidence of the cost and effectiveness of such programmes., Objective: To provide an overview of the expansion of telehealth in low- and middle-income countries amid the COVID-19 pandemic and identify the challenges, benefits, and costs associated with implementing telehealth services in these countries., Methods: We performed a literature review using the search term: '*country name* AND ((telemedicine[Title][Abstract]) OR (telehealth[Title][Abstract] OR eHealth[Title][Abstract] OR mHealth[Title][Abstract]))'. Initially, we started with 467 articles, which were reduced to 140 after filtering out duplicates and including only primary research studies. Next, these articles were screened based on established inclusion criteria and 44 articles were finalised to be used in the review., Results: We found telehealth-specific software being used as the most common tool to provide such services. Nine articles reported patient satisfaction of greater than 90% with telehealth services. Moreover, the articles identified the ability to make a correct diagnosis to resolve the condition, efficient mobilisation of healthcare resources, increased accessibility for patients, increased service utilisation, and increased satisfaction as benefits of telehealth services, whereas inaccessibility, low technological literacy, and lack of support, poor security standards and technological concerns, loss of interest by the patients, and income impacts on physicians as challenges. The review could not find articles that explored the financial information on telehealth programme implementation., Conclusion: Although telehealth services are growing in popularity, the research gap on the efficacy of telehealth is high in low- and middle-income countries. To better guide the future development of telehealth services, rigorous economic evaluation of telehealth is needed.

It is attractive to use an optical nanorouter by artificial nanostructures to substitute the traditional Bayer filter for an image array sensor, which, however, poses great challenges in balancing the design strategy and the ease of fabrication. Here, we implement and compare two inverse design schemes for rapid optimization of RGGB Bayer-type optical nanorouter. One is based on the multiple Mie scattering theory and the adjoint gradient that is applicable to arrays of nanospheres with varying sizes, and the other is based on the rigorous coupled wave analysis and the genetic algorithm. In both cases, we study layered nanostructures that can be efficiently modeled respectively which greatly accelerates the inverse design. It is shown that the color-dependent peak collection efficiencies of nanorouters designed in the two methods for red, green, and blue wavelengths reach 37%, 44%, and 45% and 52%, 50%, and 66%, respectively. We further demonstrate color nanorouters that provide light focusing to four quadrants working in both the visible and infrared bands, which promises multispectral imaging applications.

Background: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI., Methods: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively., Results: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI., Conclusions: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Objective: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure., Methods: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis., Results: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI., Conclusion: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purple Chinese cabbage (PCC) has become a new breeding trend due to its attractive color and high nutritional quality since it contains abundant anthocyanidins. With the aim of rapid evaluation of PCC anthocyanidins contents and screening of breeding materials, a fast quantitative detection method for anthocyanidins in PCC was established using Near Infrared Spectroscopy (NIR). The PCC samples were scanned by NIR, and the spectral data combined with the chemometric results of anthocyanidins contents obtained by high-performance liquid chromatography were processed to establish the prediction models. The content of cyanidin varied from 93.5 mg/kg to 12,802.4 mg/kg in PCC, while the other anthocyanidins were much lower. The developed NIR prediction models on the basis of partial least square regression with the preprocessing of no-scattering mode and the first-order derivative showed the best prediction performance: for cyanidin, the external correlation coefficient (RSQ) and standard error of cross-validation (SECV) of the calibration set were 0.965 and 693.004, respectively; for total anthocyanidins, the RSQ and SECV of the calibration set were 0.966 and 685.994, respectively. The established models were effective, and this NIR method, with the advantages of timesaving and convenience, could be applied in purple vegetable breeding practice.

The frequency of drought will increase under further warming. The increase in atmospheric CO 2 concentration, along with more frequent drought, will affect crop growth. We examined the changes of cell structure, photosynthetic physiology, antioxidant enzymes, osmotic regulatory substances, and yield of foxtail millet ( Setaria ita-lica ) leaves under different CO 2 concentrations (ambient air CO 2 concentration and ambient atmospheric CO 2 concentration + 200 μmol·mol -1 ) and water treatment (soil moisture content maintained at 45%-55%, and 70%-80% of field capacity, representing mild drought and normal water condition, respectively). The results showed that elevated CO 2 concentration increased the number of starch grains, the area of single starch grains, and the total area of starch grains in the chloroplast of millet mesophyll cells. Under mild drought condition, elevated CO 2 concentration increased net photosynthetic rate of millet leaves at the booting stage by 37.9%, but did not affect water use efficiency at this stage. Elevated CO 2 concentration increased net photosynthetic rate and water use efficiency of millet leaves under mild drought condition at the filling stage by 15.0% and 44.2%, respectively. Under mild drought condition, elevated CO 2 concentration increased the content of peroxidase (POD) and soluble sugar in millet leaves at the booting stage by 39.3% and 8.0%, respectively, but decreased proline content by 31.5%. It increased the content of POD in millet leaves at the filling stage by 26.5% but decreased the content of MDA and proline by 37.2% and 39.3%, respectively. Under mild drought condition, elevated CO 2 concentration significantly increased the number of grain spikes by 44.7% and yield by 52.3% in both years compared with normal water condition. The effect of elevated CO 2 concentration on grain yield under mild drought conditions was higher than that under normal water condition. Under mild drought conditions, elevated CO 2 concentration increased leaf thickness, vascular bundle sheath cross-sectional area, net photosynthetic rate, and water use efficiency of millet, improved the antioxidant oxidase activity, and changed the concentration of osmotic regulatory substances, alleviated the nega-tive effect of drought on foxtail millet, and finally increased the number of grains per ear and yield of foxtail millet. This study would provide a theoretical basis for millet production and sustainable agricultural development in arid areas under future climate change.

The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common. Here, we demonstrate a chemical-resistant triboelectric nanogenerator (CR-TENG) based on polysulfonamide (PSA) and polytetrafluoroethylene (PTFE) non-woven fabrics. The CR-TENG can stably harvest biological motion energy and perform intelligent safety protection monitoring in a strong corrosive environment. After treatment with strong acid and alkali solution for 7 days, the fabric morphology, diameter, tensile properties and output of CR-TENG are not affected, showing high reliability. CR-TENG integrated into protective equipment can detect the working status of protective equipment in real time, monitor whether it is damaged, and provide protection for wearers working in high-risk situations. In addition, the nonwoven-based CR-TENG has better wearing comfort and is promising for self-powered sensing in harsh environments., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

High-speed rail has been operating in more than 25 countries (mainly in Asia, Europe and North America), and has become an important part of global economic development. However, the cleaning and maintenance of high-speed rail is a comprehensive task, which may easily cause environmental pollution. This study aims to analyze and improve the sustainability of the formulation and production process of a concentrated complex enzyme detergent used as the maintenance agent for high-speed trains via the life cycle assessment (LCA) method. The eFootprint software system with built-in China, European and Swiss Ecoinvent databases was used to establish the LCA model with the system boundary being from cradle to gate. The LCA model showed that the production of 1 kg of concentrated detergent generates the global warming potential of 2.53 kg CO 2 eq, and other environmental emissions including acidification potential of 0.01 kg SO 2 eq, eutrophication potential of 3.76E-03 kg PO 4 3- eq, inhalable inorganic matter of 3.17E-03 kg PM2.5 eq, ozone depletion potential of 5.3E-06 kg CFC-11 eq, photochemical ozone formation potential of 3.44E-03 kg NMVOC eq, primary energy demand of 3.17 MJ, abiotic depletion potential of 4.97E-6 kg antimony eq, and water use of 0.84 kg. LCA results are not strongly dependent to the assumptions of the research, and the uncertainties of LCA results are between 8 and 16%, which is mainly due to the regional differences in technology sources, the year of technical data collection, and the representativeness of technology collection companies. Carbon footprint analysis showed that the production processes of enzyme stabilizer (glycerol) and surfactants contributed the most, while changes in power consumption during production and transportation distance of raw materials had limited effect on total carbon emissions. Therefore, the formulation of the concentrated complex enzymatic detergent was improved based on the LCA results. The new formulations with less enzyme stabilizer showed similar detergency to the original formulation. The new formulations could reduce carbon emissions by 5,500-9,200 tons per year and save between $4.4 and $7.4 million in annual production of 10,000 tons., Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-023-03122-2., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature B.V. 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Metal-organic frameworks (MOFs) have been proven promising in addressing many critical issues related to gas separation and purification. However, it remains a great challenge to optimize the pore environment of MOFs for purification of specific gas mixtures. Herein, we report the rational construction of three isostructural microporous MOFs with the 4,4',4"-tricarboxyltriphenylamine (H 3 TCA) ligand, unusual hexaprismane Ni 6 O 6 cluster, and functionalized pyrazine pillars [PYZ-x, x = -H (DZU-10), -NH 2 (DZU-11), and -OH (DZU-12)], where the building blocks of Ni 6 O 6 clusters and huddled pyrazine pillars are reported in porous MOFs for the first time. These building blocks have enabled the resulting materials to exhibit good chemical stability and variable pore chemistry, which thus contribute to distinct performances toward C 2 H 2 /CO 2 separation. Both single-component isotherms and dynamic column breakthrough experiments demonstrate that DZU-11 with the PYZ-NH 2 pillar outperforms its hydrogen and hydroxy analogues. Density functional theory calculations reveal that the higher C 2 H 2 affinity of DZU-11 over CO 2 is attributed to multiple electrostatic interactions between C 2 H 2 and the framework, including strong C≡C···H-N (2.80 Å) interactions. This work highlights the potential of pore environment optimization to construct smart MOF adsorbents for some challenging gas separations.

Due to maternal inheritance and minimal rearrangement, the chloroplast genome is an important genetic resource for evolutionary studies. However, the evolutionary dynamics and phylogenetic performance of chloroplast genomes in closely related species are poorly characterized, particularly in taxonomically complex and species-rich groups. The taxonomically unresolved Ficus sarmentosa species complex (Moraceae) comprises approximately 20 taxa with unclear genetic background. In this study, we explored the evolutionary dynamics, hotspot loci, and phylogenetic performance of thirteen chloroplast genomes (including eleven newly obtained and two downloaded from NCBI) representing the F. sarmentosa complex. Their sequence lengths, IR boundaries, repeat sequences, and codon usage were compared. Both sequence length and IR boundaries were found to be highly conserved. All four categories of long repeat sequences were found across all 13 chloroplast genomes, with palindromic and forward sequences being the most common. The number of simple sequence repeat (SSR) loci varied from 175 (F. dinganensis and F. howii) to 190 (F. polynervis), with the dinucleotide motif appearing the most frequently. Relative synonymous codon usage (RSCU) analysis indicated that codons ending with A/T were prior to those ending with C/T. The majority of coding sequence regions were found to have undergone negative selection with the exception of ten genes (accD, clpP, ndhK, rbcL, rpl20, rpl22, rpl23, rpoC1, rps15, and rps4) which exhibited potential positive selective signatures. Five hypervariable genic regions (rps15, ycf1, rpoA, ndhF, and rpl22) and five hypervariable intergenic regions (trnH-GUG-psbA, rpl32-trnL-UAG, psbZ-trnG-GCC, trnK-UUU-rps16 and ndhF-rpl32) were identified. Overall, phylogenomic analysis based on 123 Ficus chloroplast genomes showed promise for studying the evolutionary relationships in Ficus, despite cyto-nuclear discordance. Furthermore, based on the phylogenetic performance of the F. sarmentosa complex and F. auriculata complex, the chloroplast genome also exhibited a promising phylogenetic resolution in closely related species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Zhuo (Adam) Chen is on the Chinese Medical Board and has no competing interests. April Moreno, Bei Wu, Celine Nguyen, Elle Lett, Leena Yin, Monica McLemore, Raynald Samoa and Wanda Montalvo have no competing interests. Donglan “Stacy” Zhang has received support from the Chinese Economist Society, the Calvin J Li Memorial Foundation, the Center for Reducing health Disparities at the University of Nebraska Medical Center and from NIH Grant ROI MD01 3886. Cite this article as: McLemore M, Chen Z, Lett E, Samoa R, Moreno A, Wu B, Yin L, Zhang D, Montalvo W, Nguyen C (2022) Fireside chat on the Asian American, Native Hawaiian, and Pacific Islander special edition of the Health Equity journal featuring authors, Health Equity 6:1, 953–964, DOI: 10.1089/heq.2022.29016.rtd.

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group ( n =10) , poisoned group ( n =40) and treatment groups ( n =200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 μmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant ( P =0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant ( P =0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant ( P =0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

Purpose: To investigate the effect of shikonin (SKN) on proliferation, apoptosis, migration and angiogenesis of hemangioma endothelial cell (HemEC)., Methods: CCK-8 and EdU assays were used to detect the effect of SKN on proliferation of HemEC. The effect of SKN on apoptosis of HemEC was detected by flow cytometry. Wound healing assay was used to detect the effect of SKN on migration ability of HemEC. The effect of SKN on angiogenesis ability of HemEC was detected by tube formation assay. SPSS 22.0 software package was used for statistical analysis of the data., Results: SKN inhibited proliferation (P＜0.001) and promoted apoptosis (P＜0.001) of HemEC in a concentration-dependent manner. In additon, SKN inhibited HemEC migration(P＜0.01) and angiogenesis(P＜0.001)., Conclusions: SKN can inhibit proliferation, migration, angiogenesis and promote apoptosis of HemEC.

In this study, a couple of tetradentate Pt(II) enantiomers ((-)- 1 and (+)- 1 ) and a couple of tetradentate Pt(IV) enantiomers ((-)- 2 and (+)- 2 ) containing fused 5/6/6 metallocycles have been synthesized by controlling reaction conditions. Two valence forms could transform into each other through mild chemical oxidants and reductants. Single-crystal X-ray diffraction confirms the structures of (-)-1 and (-)-2. The coordination sphere of the Pt(II) cation in (-)- 1 displays a distorted square-planar geometry and a platinum centroid helix chirality. In contrast, the structure of (-)- 2 reveals a distorted octahedral geometry. The solution and the solid of (-)- 1 are highly luminescent. Complex (-)- 1 shows a prominent aggregation-induced emission enhancement (AIEE) behavior in DMSO/water solution with emission quantum yield ( Φ em ) up to 73.2%. Furthermore, highly phosphorescent Pt(II) enantiomers exhibit significant circularly polarized luminescence (CPL) with a dissymmetry factor ( g lum ) of order 10 -3 in CH 2 Cl 2 solutions at room temperature. Symmetrically appreciable CPL signals are observed for the enantiomers (-)- 1 and (+)- 1 ., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Purpose: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC)., Patients and Methods: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription., Results: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only., Conclusions: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation., (©2022 The Authors; Published by the American Association for Cancer Research.)

A new climbing species, Ficusmotuoensis Zhen Zhang & Hong Qing Li in Moraceae from southwest China has been described and illustrated in this paper. The new species resembles F.disticha , F.diversiformis and F.hederacea , but differs from these in the medium-sized acrophylls, shorter peduncle, as well as larger and spotted syconium. According to the morphological traits and phylogenetic placement, the new species belongs to Ficussubg.Synoeciasect.Apiosycea. Besides, the new species deviates from the common distribution pattern compared to the other members of sect. Apiosycea, indicating that it could be very useful for exploring the biogeography of sect. Apiosycea., (Zhen Zhang, Mei-Jiao Zhang, Jian-Hang Zhang, De-Shun Zhang, Hong-Qing Li.)

Ficus sarmentosa is a common climbing fig tree in East Asia in Moraceae, and its particular geographical distributed pattern and on-going radiation evolution make it significant to explore evolutionary history and biogeography of Ficus . In this work, the first complete chloroplast genome of F. sarmentosa was reported using Illumina NovaSeq high-throughput sequencing data. Totally, the whole chloroplast genome of F. sarmentosa is 160,183 bp in length, which includes large single-copy region of 88,307 bp, small single-copy region of 20,080 bp, and two pairs of inverted repeat regions of 25,898 bp. In addition, GC content and microsatellite makers of the genome were explored. Lastly, phylogenetic analysis demonstrated the closest relationship between F. sarmentosa and F. pumila ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Deficient mismatch repair (dMMR) or the microsatellite instability (MSI) phenotype occupied approximately 15-18% of CRC patients. Previous studies showed that dMMR/MSI status is a favorable prognostic factor for stage II/III CRC patients. For metastatic colorectal cancer (mCRC) patients, only 5% of patients have the dMMR/MSI-H phenotype. The relationship between dMMR/MSI, chemosensitivity and survival in mCRC patients of real-world is still not clear. Materials and methods: In this study, we enrolled 77 dMMR/MSI-H mCRC patients and compared their clinicopathological characteristics with those of 510 proficient MMR (pMMR) or microsatellite stable (MSS) mCRC patients. With propensity score matching (PSM) analysis, we further compared the chemosensitivity and survival of dMMR/MSI-H mCRC patients with pMMR/MSS patients. We also analyzed the efficacy of different chemotherapy and target therapy in the dMMR/MSI-H population. Results: In PSM cohort, the objective response rate (ORR) of mCRC patients with dMMR/MSI-H undergoing first-line palliative chemotherapy was 35.2%, which was similar with patients with pMMR/MSS (35.4%, p = 1.00). The median progression-free survival (PFS) of first-line chemotherapy was significantly different (dMMR/MSI-H vs pMMR/MSS = 7.4 months vs 10.2 months; HR = 0.74; 95%CI, 0.57-0.98; p = 0.03). Overall survival (OS) of patients did not significantly differ by status (dMMR/MSI-H vs pMMR/MSS = 40.0 months vs 41.3 months; HR = 1.09; 95%CI, 0.74-1.59; p = 0.68). For second-line palliative chemotherapy, there was no difference in ORR ( p = 0.53) or in PFS (HR = 0.88; 95%CI, 0.59-1.33; p = 0.56) between dMMR/MSI-H and pMMR/MSS tumors. We also found that in the overall cohort, the ORR of patients who received oxaliplatin-based and irinotecan-based chemotherapy were 28.8% and 54.5%, respectively, which were not significantly different ( p = 0.16). Our results also showed that the use of bevacizumab could lead to a significantly higher ORR in dMMR/MSI-H mCRC patients compared to chemotherapy alone (55.0% vs 22.2%; p = 0.02), whereas cetuximab could not. Conclusion: The dMMR/MSI-H is not a prognostic factor for mCRC patients but is correlated with shorter PFS to first-line palliative chemotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses., Methods: Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice., Results: Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05)., Conclusion: A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4) are widely used to assess liver fibrosis in chronic hepatitis B virus (HBV) infection. Currently, the definition of normal alanine aminotransferase (ALT) is controversial. We aimed to examine the diagnostic value of APRI and FIB-4 in chronic HBV carriers with different upper limits of normal (ULNs) for ALT., Methods: 581 chronic HBV carriers were divided into the following four groups based on different ULNs for ALT: chronic HBV carriers I, II, III, and IV. Furthermore, 106 chronic HBV carriers formed an external validation group. Predictive values of APRI and FIB-4 were elucidated using the area under the curve (AUC). A liver fibrosis-predictive model-GPSA (named for its measure of gamma glutamyl transpeptidase, platelet count, HBsAg and albumin) was developed using multivariate logistic regression analysis., Results: In chronic HBV carriers I, the AUCs of APRI and FIB-4 were 0.680 and 0.609 for significant fibrosis and 0.678 and 0.661 for cirrhosis, respectively. The AUCs of GPSA for significant fibrosis in the training group, internal group, and external validation group were 0.877, 0.837, and 0.871, respectively. The diagnostic value of GPSA differed among chronic HBV carriers I, II, III, and IV, with AUCs for significant fibrosis being 0.857, 0.853, 0.868, and 0.905 and AUCs for cirrhosis being 0.901, 0.905, 0.886, and 0.913, respectively. GPSA showed a higher diagnostic value than APRI and FIB-4 for predicting significant fibrosis in the four groups., Conclusions: The GPSA model allows for accurate diagnosis of liver fibrosis in chronic HBV carriers with different ULN for ALT., Competing Interests: The authors have no conflict of interests related to this publication., (© 2022 Authors.)

Purpose: This study aims to explore the differences in mental health status among Asian Americans during the COVID-19 pandemic., Methods: Data from the 2020 Health, Ethnicity, and Pandemic (HEAP) Study were used to explore the psychological distress of 2672 adults, using the Standard Kessler Psychological Distress Scale., Results: We observed that among Asian American subgroups, South Asian Americans had significantly higher odds of experiencing psychological distress than non-Hispanic White Americans (odds ratio = 1.82, 95% confidence interval = 1.00-3.31), after controlling for covariates., Conclusion: The study identified differences in mental health status among Asian American subgroups. We recommend the implementation of culturally appropriate interventions to help Asian Americans cope with mental health challenges., Competing Interests: No competing financial interests exist., (© Biplav Babu Tiwari and Donglan “Stacy” Zhang 2022; Published by Mary Ann Liebert, Inc.)

Cerebral infarction, a common central nervous system complication after adult cardiac surgery, is one of the main factors leading to the poor prognosis of cardiac surgery patients besides cardiac insufficiency. However, there is currently no effective treatment for cerebral infarction. Therefore, early prevention and diagnosis of postoperative cerebral infarction are particularly important. There are many factors and mechanisms during and after cardiac surgery that play an important role in the occurrence of postoperative cerebral infarction, such as intraoperative embolism, systemic inflammatory response syndrome, atrial fibrillation, temperature regulation, blood pressure control, use of postoperative blood products, and so forth. The mechanism by which most risk factors act on the human body, leading to postoperative cerebral infarction, is not well understood, and further research is needed. Therefore, this paper aims to summarize and explain the relevant risk factors, mechanisms, clinical signs, imaging characteristics, and early diagnosis methods of cerebral infarction complications after cardiac surgery, and provides useful data for the establishment of related diagnosis and treatment standards., Competing Interests: The author declares no conflicts of interest., (© 2022 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)