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Ming Li,1,&ast; Da-Ming Xu,1,&ast; Shu-Bin Lin,1 Zheng-Liang Yang,1 Teng-Yu Xu,1 Jin-Huan Yang,1 Ze-Xin Lin,1 Ze-Kai Huang,1 Jun Yin2,3 1Division of Urological Surgery, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 2Division of Hematology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun YinDepartment of Clinical Laboratory Medicine and Division of Hematology, The Second Affiliated Hospital of Shantou University Medical College, Dongxia Road North, Shantou, Guangdong Province, 515041, People’s Republic of ChinaTel +86 754 8891 5950Email jyin@stu.edu.cnObjective: To investigate the immune profiles in benign prostatic hyperplasia, changes in the absolute number of lymphocyte subsets and the proportion of T lymphocyte subsets were detected.Methods: Absolute value of lymphocyte subsets in peripheral blood (T, B and NK cells) and the proportion of T lymphocyte (native CD4+ T cell, memory CD4+ T cell, CD8+CD28+ T cell, CD8+CDDR+ T cells and CD8+CD38+ T cell) were measured by flow cytometry.Results: The absolute values of CD3+ T cell (972.55± 330.31 vs 1757.99± 439.38), CD4+ T cell (656.43± 252.39 vs 899.30± 262.10), and CD8+ T cell (301.97± 147.76 vs 728.45± 230.34) in patients with benign prostatic hyperplasia were significantly reduced (all P< 0.05). There was no significant difference in NK cell (285.58± 182.84 vs 528.92± 208.17) and B cell (186.66± 86.62 vs 334.17± 130.46). The proportion of naive CD4+ T cell (3.75± 0.50 vs 8.54± 1.61) in T lymphocyte subsets in patients with BPH was significantly reduced (P< 0.05). There was no significant difference in memory CD4+ T cell (87.9± 6.37 vs 92.63± 5.94), CD8+CD28+ T cell (60.52± 13.86 vs 64.32± 12.78), CD8+CDDR+ T cell (36.58± 12.87 vs 31.92± 8.54) and CD8+CD38+ T cell (2.1± 1.90 vs 2.55± 2.01).Conclusion: Immune dysfunction raised the risk of viral infection, inflammatory stimulation, and tumor induction in prostate cells, leading to hyperplasia, and immune non-response was potentially a key factor in the transformation of BPH into prostate cancer.Keywords: benign prostatic hyperplasia, lymphocyte subsets, pathogenesis, flow cytometry

Zhi-Bi Zhang,1 Tian-Yong Xu,2 Ding-Yun You,3 Shuai Yi,4 Qing Liu,4 Huifang-Jie Li,4 Jin-Yun Gu5 1Biomedical Engineering Center, Kunming Medical University, Kunming, People’s Republic of China; 2Experiment Center for Medical Science Research, Kunming, People’s Republic of China; 3Department of Science and Technology, Kunming Medical University, Kunming, People’s Republic of China; 4School of Forensic Medicine, Kunming Medical University, Kunming, People’s Republic of China; 5Zhanyi Branch of Qujing Public Security Bureau, Qujing, People’s Republic of China Background: A number of studies have demonstrated the significant and rapid antidepressant effects of ketamine, which is also known as a neurotoxic and illicit drug. Ketamine and alcohol are increasingly used together in clubs by teenagers and young adults. Previous studies have proven that chronic ketamine consumption induces a delayed and persistent activation of the dopamine (DA) system. However, the rewarding properties of recreational ketamine abuse remain unclear, and the underlying mechanisms of the effects on the DA system after administration of ketamine with ethanol are yet to be explored. Methods: Here, we evaluated the effects of two different doses of ketamine (30 mg/kg and 60 mg/kg) with and without ethanol (0.3156 g/kg) on DA concentration in the rat’s ventral tegmental area (VTA), a vital region in the reward and motivation system. We explored the effects of the combined drug treatment on the expression profiling of the DA metabolism genes, tyrosine hydroxylase, dopa decarboxylase, vesicular monoamine transporter 2, and synaptosomal-associated protein 25, as well as protein expression level of brain-derived neurotrophic factor in the rat’s VTA. Results: We found that administration of ketamine with ethanol led to a significant increase of DA in the VTA associated with differential regulation of mRNA levels of the four DA metabolism genes and protein levels of brain-derived neurotrophic factor. Moreover, the rewarding properties of coadministration of ketamine and ethanol were related to dopaminergic neuron activation in the VTA. Conclusion: These results indicated the possibility that combined drug treatment might positively affect the mesencephalic DA reward system. Keywords: ketamine, ethanol, TH, DDC, dopamine, ventral tegmental area

Liang Qin,1,* Tianyuan Xu,1,* Leilei Xia,1 Xianjin Wang,1 Xiang Zhang,1 Xiaohua Zhang,1 Zhaowei Zhu,1 Shan Zhong,1 Chuandong Wang,2 Zhoujun Shen1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: It has been demonstrated that chloroquine (CQ) enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC). In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo.Methods: The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy.Results: The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P

Whether the well-known metabolic switch AMP-activated protein kinase (AMPK) is involved in the insulin-sensitizing effect of calorie restriction (CR) is unclear. In this study, we investigated the role of AMPK in the insulin-sensitizing effect of CR in skeletal muscle. Wild-type (WT) and AMPK-α2(-/-) mice received ad libitum (AL) or CR (8 weeks at 60% of AL) feeding. CR increased the protein level of AMPK-α2 and phosphorylation of AMPK-α2. In WT and AMPK-α2(-/-) mice, CR induced comparable changes of body weight, fat pad weight, serum triglycerides, serum nonesterified fatty acids, and serum leptin levels. However, decreasing levels of fasting/fed insulin and fed glucose were observed in WT mice but not in AMPK-α2(-/-) mice. Moreover, CR-induced improvements of whole-body insulin sensitivity (evidenced by glucose tolerance test/insulin tolerance test assays) and glucose uptake in skeletal muscle tissues were abolished in AMPK-α2(-/-) mice. Furthermore, CR-induced activation of Akt-TBC1D1/TBC1D4 signaling, inhibition of mammalian target of rapamycin-S6K1-insulin receptor substrate-1 pathway, and induction of nicotinamide phosphoribosyltransferase-NAD(+)-sirtuin-1 cascade were remarkably impaired in AMPK-α2(-/-) mice. CR serum increased stability of AMPK-α2 protein via inhibiting the X chromosome-linked ubiquitin-specific protease 9-mediated ubiquitylation of AMPK-α2. Our results suggest that AMPK may be modulated by CR in a ubiquitylation-dependent manner and acts as a chief dictator for the insulin-sensitizing effects of CR in skeletal muscle. [ABSTRACT FROM AUTHOR]

Whether left ventricular structure and function is associated with sodium dietary intake and renal handling while considering blood pressure (BP) remains unclear. Consecutive untreated patients referred for ambulatory BP monitoring were recruited. Standard echocardiography was performed to measure left ventricular structure and function. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal tubular sodium handling, respectively. The 952 participants (51.0% women; mean age, 50.8 years) included 614 (64.5%) ambulatory hypertension and 103 (10.8%) left ventricular hypertrophy. There were significant interactions of urinary sodium excretion with FELi (P ≤ 0.045), but not FDRNa (P ≥ 0.36), in relation to left ventricular posterior wall thickness (LVPW), mass (LVM) and mass index (LVMI), but not functional measurements. Only in tertile 1 of FELi, the multivariate-adjusted regression coefficients for urinary sodium excretion reached statistical significance (P ≤ 0.049), being 0.16 ± 0.05 mm, 4.32 ± 1.48 g, and 1.64 ± 0.83 g/m 2 for LVPW, LVM and LVMI, respectively. In mutually adjusted analyses, the regression coefficient for LVMI was statistically significant for FELi, FDRNa and 24-h systolic BP, being -2.17 ± 0.49, -1.95 ± 0.54, and 2.99 ± 0.51 g/m 2 , respectively (P < 0.001). Multivariable analysis of variance showed that sodium renal handling indexes (P ≥ 0.14), but not sodium urinary excretion (P = 0.007), were similarly as 24-h BP associated with LVMI. Heat maps on left ventricular hypertrophy provided a graphical confirmation of the findings. Sodium dietary intake and renal handling interact to be associated with left ventricular structure. Renal handling indexes were similarly in size as, jointly in action with and independently of 24-h BP., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

In recent years, alkaline soda soil has stimulated numerous biological research on plants under carbonate stress. Here, we explored the difference in physiological regulation of rice seedlings between saline (NaCl) and alkaline carbonate (NaHCO3 and Na2 CO3 ) stress. The rice seedlings were treated with 40mM NaCl, 40mM NaHCO3 and 20mM Na2 CO3 for 2h, 12h, 24h and 36h, their physiological characteristics were determined, and organic acid biosynthesis and metabolism and hormone signalling were identified by transcriptome analysis. The results showed that alkaline stress caused greater damage to their photosynthetic and antioxidant systems and led to greater accumulation of organic acid, membrane damage, proline and soluble sugar but a decreased jasmonic acid content compared with NaCl stress. Jasmonate ZIM-Domain (JAZ), the probable indole-3-acetic acid-amido synthetase GH3s, and the protein phosphatase type 2Cs that related to the hormone signalling pathway especially changed under Na2 CO3 stress. Further, the organic acid biosynthesis and metabolism process in rice seedlings were modified by both Na2 CO3 and NaHCO3 stresses through the glycolate/glyoxylate and pyruvate metabolism pathways. Collectively, this study provides valuable evidence on carbonate-responsive genes and insights into the different molecular mechanisms of saline and alkaline stresses.

Objectives: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS., Methods: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage., Results: We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress., Conclusions: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.

Background: This study explored risk perception characteristics and influencing factors among informal caregivers of functionally dependent elderly individuals at home, aiming to improve caregivers' caregiving risk perception and coping abilities and ultimately enhance the quality of life for these individuals., Methods: We used purposive sampling to select 22 informal caregivers from a community in Zhengzhou City, Henan Province, China, between March and September 2023 and conducted face-to-face semi-structured in-depth interviews. The data were analyzed using Colaizzi's seven-step analysis method., Results: We extracted two themes, caregiving risk perception characteristics and caregiving risk perception associated factors, and eight sub-themes, perceived risk possibility, perceived risk anticipation, perceived severity of consequences, past caregiving experiences, health literacy, psychological status, caregiving burden, and family social support., Conclusion: There were differences in how informal caregivers perceived the risks associated with caring for functionally dependent elderly individuals at home, which various factors could influence. It was essential to provide training that covered the knowledge and skills needed for caregiving, improve caregivers' awareness of safety risks, and establish a correct perception of caregiving risks. The government must construct and refine a comprehensive framework for caregiver respite services. Simultaneously, healthcare professionals should proactively undertake health education endeavors to augment the recognition of care safety risks among informal caregivers, thereby cultivating an accurate awareness of care risk perception., (© 2024. The Author(s).)

Harnessing the photoinduced phase transitions in organic crystals, especially the changes in shape and structure across various dimensions, offers a fascinating avenue for exact spatiotemporal control, which is crucial for developing future smart devices. In our study, we report a new photoactive molecular crystal made from ( E )-2-(3-phenyl-allylidene)malonate (( E )-PADM). When exposed to ultraviolet (UV) light at 365 nm, this compound experiences an E -to- Z photoisomerization in liquid solution and a crystal-to-liquid phase transition in solid crystals. Remarkably, nanoscopic crystalline rods boost their melting rate and degree compared to bulk crystals, indicating that miniaturization enhances the photoinduced melting effect. Our results demonstrate a simple approach to rapidly drive molecular crystals into liquids via photochemical reactions and phase transitions.

Since the 1970s, artificial intelligence (AI) has played an increasingly pivotal role in the medical field, enhancing the efficiency of disease diagnosis and treatment. Amidst an aging population and the proliferation of chronic disease, the prevalence of complex surgeries for high-risk multimorbid patients and hard-to-heal wounds has escalated. Healthcare professionals face the challenge of delivering safe and effective care to all patients concurrently. Inadequate management of skin wounds exacerbates the risk of infection and complications, which can obstruct the healing process and diminish patients' quality of life. AI shows substantial promise in revolutionizing wound care and management, thus enhancing the treatment of hospitalized patients and enabling healthcare workers to allocate their time more effectively. This review details the advancements in applying AI for skin wound assessment and the prediction of healing timelines. It emphasizes the use of diverse algorithms to automate and streamline the measurement, classification, and identification of chronic wound healing stages, and to predict wound healing times. Moreover, the review addresses existing limitations and explores future directions., Competing Interests: None., (AJTR Copyright © 2024.)

Herein, two atomically precise silver nanoclusters, Ag54 and Ag33, directed by inner anion templates (CrO 4 2- and/or Cl - ), are initially isolated as a mixed phase from identical reactants across a wide temperature range (20-80 °C). Interestingly, fine-tuning the reaction temperature can realize pure phase synthesis of the two nanoclusters; that is, a metastable Ag54 is kinetically formed at a low temperature (20 °C), whereas such a system is steered towards a thermodynamically stable Ag33 at a relatively high temperature (80 °C). Electrospray ionization mass spectrometry illustrates that the stability of Ag33 is superior to that of Ag54, which is further supported by density functional theory calculations. Importantly, the difference in structural stability can influence the pathway of 1,4-bis(pyrid-4-yl)benzene induced transformation reaction starting from Ag54 and Ag33. The former undergoes a dramatic breakage-reorganization process to form an Ag 31 dimer (Ag31), while the same product can be also achieved from the latter following a noninvasive ligand exchange process. Both the Ag54 and Ag33 have the potential for further remote laser ignition applications. This work not only demonstrates how temperature controls the isolation of a specific phase, but also sheds light on the structural transformation pathway of nanoclusters with different stability., (© 2024 Wiley-VCH GmbH.)

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering., (© 2024 Wiley‐VCH GmbH.)

We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients., (© 2024. Huazhong University of Science and Technology.)

Background: The quality of transitional care is closely related to the health outcomes of patients, and understanding the status of transitional care for patients is crucial to improving the health outcomes of patients. Therefore, this study aims to investigate the quality of transitional care in elderly patients with chronic diseases and analyze its influencing factors, to provide a basis for improving transitional care services., Methods: This is a cross-sectional study. We used the Chinese version of the Partners at Care Transitions Measure (PACT-M) to survey patients with chronic diseases aged 60 years and older who were about to be discharged from five tertiary hospitals in Henan and Shanxi provinces. We used the mean ± standard deviation to describe the quality of transitional care, t-test or one-way ANOVA, and regression analysis to explore the factors affecting the quality of transitional care for patients., Results: 182 elderly patients with chronic diseases aged ≥ 60 years completed the PACT-M survey. The scores of PACT-M 1 and PACT-M 2 were (30.69 ± 7.87) and (25.59 ± 7.14) points, respectively. The results of the t-test or one-way ANOVA showed that the patient's marital status, ethnicity, religion, educational level, preretirement occupation, residence, household income per month, and living situation had an impact on the quality of transitional care for elderly patients with chronic diseases (P < 0.05). The results of regression analyses showed that patients' preretirement occupation, social support, and health status were the main influences on the quality of transitional care for elderly patients with chronic diseases (P < 0.05), and they explained 63.1% of the total variance., Conclusions: The quality of transitional care for older patients with chronic illnesses during the transition from hospital to home needs further improvement. Factors affecting the quality of transitional care included patients' pre-retirement occupation, social support, and health status. We can improve the hospital-community-family tertiary linkage service to provide coordinated and continuous transitional care for patients based on their occupation, health status, and social support to enhance the quality of transitional care and the patient's health., (© 2024. The Author(s).)

Background: The effect of pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) have not been reported previously in kidney renal clear cell carcinoma (KIRC) patients and thus we made a comprehensive analysis of pain genes in the prognosis of KIRC and tumor immunotherapy., Methods: In this study, TCGA, Kaplan-Meier plotter, Metascape, STRING, Human Protein Atlas, Single Cell Expression Atlas database, LinkedOmics, cBioPortal, MethSurv, CancerSEA, COSMIC database and R package (ggplot2, version 3.3.3) were used for comprehensive analysis of pain genes in KIRC. Pearson and Spearman correlation coefficients were for co-expression analysis. Immunotherapy and TISIDB database were used for tumor Immunotherapy., Results: Representative pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4) were statistically significant ( p  < 0.0001) in the prognosis of KIRC. Immunotherapy (anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA4 therapy) and immunomodulator (immunoinhibitor, immunostimulator, and MHC molecule) in KIRC were significant associated with pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4), which were the important addition to clinical decision making for patients., Conclusions: Our study uncovered a mechanism for the effect of pain genes on KIRC outcome via the modulation of associated co-expression gene networks, gene variation, and tumor Immunotherapy., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Stable viologen-derived multifunctional smart materials exhibit widespread practical applications in many areas. In this study, a viologen-derived material with 4-fold interpenetrating diamondoid network, {[Cd(1,4-ndc)(cpbpy)]·2H 2 O} n , was successfully constructed based on asymmetrical N-(3-carboxyphenyl)-4,4'-bipyridinium (cpbpy) and 1,4-naphthalenedicarboxylic acid (1,4-H 2 ndc). The compound shows reversible photochromic behavior under a xenon lamp, which are proved by UV-vis spectra and EPR characterizations. Moreover, the compound with good photoluminescence properties displays photocontrolled luminescence quenching behaviors. Owing to its good water stability, the compound is then applied in luminescence sensing for the detection of Cr 2 O 7 2- in aqueous solution. The corresponding luminescence quenching constant for Cr 2 O 7 2- is K SV  = 4.33 × 10 4 M -1 , and the detection limit is 3.66 μM. Systematic investigations on the luminescence quenching mechanism suggest that the inner filter effect resulted in the selective detection of Cr 2 O 7 2- . This study provides inspiration for the design and synthesis of target luminescent crystalline materials with rigid and asymmetric viologen-derived ligands., 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.)

We investigated the potential diagnostic value of the myocardial work indices based on speckle tracking echocardiography for cardiac fibrosis in patients with primary aldosteronism. Our observational study included 48 patients with primary aldosteronism. We performed conventional echocardiography and the left ventricular pressure-strain loop analysis. We also performed cardiac magnetic resonance imaging to evaluate cardiac replacement fibrosis defined as late gadolinium enhancement (LGE). Patients with LGE (n = 30, 62.5%) had longer duration of hypertension and higher plasma NT-proBNP than those without LGE. Besides, they had a significantly (P ≤ 0.04) higher left ventricular mass index (121.3 ± 19.5 vs. 103.3 ± 20.0 g/m 2 ) and global wasted work (205 ± 78 vs. 141 ± 36 mmHg%) and lower global longitudinal strain (-17.7 ± 1.8 vs. -19.0 ± 2.4%) and work efficiency (GWE, 90.9 ± 2.4 vs. 93.8 ± 1.5%). Receiver Operating Characteristics analysis showed that GWE ≤ 92% had a sensitivity and specificity of 76.7% and 83.3%, respectively, for LGE with the area under curve 0.85 (P < 0.001). In conclusion, both cardiac structure and function were impaired in patients with primary aldosteronism and cardiac fibrosis. The myocardial work index GWE showed significant value for the indication of cardiac fibrosis. Characterization of cardiac fibrosis in primary aldosteronism and the detective value of clinical and echocardiographic indices. Cardiac fibrosis was presented in 30 of the 48 analyzed primary aldosteronism patients with focal high signal intensity in mid-layer myocardium in limited segments as its characterization. The global work efficiency (GWE) had a significantly higher detective value for myocardial replacement fibrosis than other measurements such as left ventricular mass index (LVMI) and NT-proBNP., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Meteorin-like (Metrnl) is a novel secreted protein with various biological activities. In this study, we investigated whether and how Metrnl regulated skin wound healing in mice. Global Metrnl gene knockout mice (Metrnl -/- ) and endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl -/- ) were generated. Eight-mm-diameter full-thickness excisional wound was made on the dorsum of each mouse. The skin wounds were photographed and analyzed. In C57BL/6 mice, we observed that Metrnl expression levels were markedly increased in skin wound tissues. We found that both global and endothelial cell-specific Metrnl gene knockout significantly retarded mouse skin wound healing, and endothelial Metrnl was the key factor affecting wound healing and angiogenesis. The proliferation, migration and tube formation ability of primary human umbilical vein endothelial cells (HUVECs) were inhibited by Metrnl knockdown, but significantly promoted by addition of recombinant Metrnl (10 ng/mL). Metrnl knockdown abolished the proliferation of endothelial cells stimulated by recombinant VEGFA (10 ng/mL) but not by recombinant bFGF (10 ng/mL). We further revealed that Metrnl deficiency impaired VEGFA downstream AKT/eNOS activation in vitro and in vivo. The damaged angiogenetic activity in Metrnl knockdown HUVECs was partly rescued by addition of AKT activator SC79 (10 μM). In conclusion, Metrnl deficiency retards skin wound healing in mice, which is related to impaired endothelial Metrnl-mediated angiogenesis. Metrnl deficiency impairs angiogenesis by inhibiting AKT/eNOS signaling pathway., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Posttranslational modification dramatically enhances protein complexity, but the function and precise mechanism of novel lysine acylation modifications remain unknown. Chemoresistance remains a daunting challenge to successful treatment. We found that lysine butyrylation (Kbu) is specifically upregulated in chemoresistant tumor cells and tissues. By integrating butyrylome profiling and gain/loss-of-function experiments, lysine 754 in HSP90 (HSP90 K754) was identified as a substrate for Kbu. Kbu modification leads to overexpression of HSP90 in esophageal squamous cell carcinoma (ESCC) and its further increase in relapse samples. Upregulation of HSP90 contributes to 5-FU resistance and can predict poor prognosis in cancer patients. Mechanistically, HSP90 K754 is regulated by the cooperation of KAT8 and HDAC11 as the writer and eraser, respectively; SDCBP increases the Kbu level and stability of HSP90 by binding competitively to HDAC11. Furthermore, SDCBP blockade with the lead compound V020-9974 can target HSP90 K754 to overcome 5-FU resistance, constituting a potential therapeutic strategy., (© 2023. The Author(s).)

Aim: To compare the clinical efficacy and safety of ultrasonic cycloplasty (UCP) vs Ahmed glaucoma drainage valve implantation (ADV) in addition to intravitreal anti-vascular endothelial growth factor (VEGF) for treatment of fundus disease-related neovascular glaucoma (NVG)., Methods: A total of 43 patients (45 eyes) with NVG secondary to fundus diseases underwent anti-VEGF combined with UCP or ADV from August 2020 to March 2022 were enrolled in this retrospective cohort study. Of them, 14 patients (15 eyes) were treated with both UCP and anti-VEGF as the UCP group and 29 patients (30 eyes) treated with both ADV and anti-VEGF as the ADV group. The success of the treatment was defined as intraocular pressure (IOP) between 11-20 mm Hg with or without using IOP-lowering drugs. IOP measurement, IOP lowering drugs at baseline and follow-ups period and complications were recorded., Results: The average age was 63.03±9.95 and 52.27±12.89y in ADV and UCP groups, respectively ( P =1.947). The fundus pathology included proliferative diabetic retinopathy in 42 eyes and retinal vein occlusion in 3 eyes. All eyes in both groups achieved successful treatment at 3mo. While the success rate was 90.0% (27/30) in the ADV group and 86.7% (13/15) in the UCP group at the last follow-up of 6mo ( P >0.05). IOP was significantly lower with reduction of drug use than the baseline in both groups (both P <0.05). And the ADV group needed fewer anti-glaucoma drops than the UCP group from 1d to 3mo. The comfort scores of patients in the ADV group were significantly lower than those in the UCP group in the first week after the operation ( P <0.05)., Conclusion: UCP is an alternative to the ADV with the same efficacy but non-invasive for the treatment of NVG., (International Journal of Ophthalmology Press.)

Significance: Metastatic cancer cells upregulate ANO1 to activate cell-intrinsic and -extrinsic mechanisms that alter cholesterol metabolism and stimulate fibroblasts, which can be targeted with ANO1 inhibitors to inhibit metastatic growth. See related commentary by Singh and Mehla, p. 1759., (©2023 American Association for Cancer Research.)

There is some evidence that nighttime blood pressure varies between seasons. In the present analysis, we investigated the seasonal variation in ambulatory nighttime blood pressure and its associations with target organ damage. In 1054 untreated patients referred for ambulatory blood pressure monitoring, we performed measurements of urinary albumin-to-creatinine ratio (ACR, n = 1044), carotid-femoral pulse wave velocity (cfPWV, n = 1020) and left ventricular mass index (LVMI, n = 622). Patients referred in spring (n = 337, 32.0%), summer (n = 210, 19.9%), autumn (n = 196, 18.6%) and winter (n = 311, 29.5%) had similar 24-h ambulatory systolic/diastolic blood pressure (P ≥ 0.25). However, both before and after adjustment for confounding factors, nighttime systolic/diastolic blood pressure differed significantly between seasons (P < 0.001), being highest in summer and lowest in winter (adjusted mean values 117.0/75.3 mm Hg vs. 111.4/71.1 mm Hg). After adjustment for confounding factors, nighttime systolic/diastolic blood pressure were significantly and positively associated with ACR, cfPWV and LVMI (P < 0.006). In season-specific analyses, statistical significance was reached for all the associations of nighttime blood pressure with target organ damage in summer (P ≤ 0.02), and for some of the associations in spring, autumn and winter. The association between nighttime systolic blood pressure and ACR was significantly stronger in patients examined in summer than those in winter (standardized β, 0.31 vs 0.11 mg/mmol, P for interaction = 0.03). In conclusion, there is indeed seasonality in nighttime blood pressure level, as well as in its association with renal injury in terms of urinary albumin excretion. Our study shows that there is indeed seasonal variability in nighttime blood pressure, highest in summer and lowest in winter, and its association with renal injury in terms of urinary albumin excretion varies between summer and winter as well., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Posttranslational modifications add tremendous complexity to proteomes; however, gaps remain in knowledge regarding the function and regulatory mechanism of newly discovered lysine acylation modifications. Here, we compared a panel of non-histone lysine acylation patterns in metastasis models and clinical samples, and focused on 2-hydroxyisobutyrylation (Khib) due to its significant upregulation in cancer metastases. By the integration of systemic Khib proteome profiling in 20 paired primary esophageal tumor and metastatic tumor tissues with CRISPR/Cas9 functional screening, we identified N-acetyltransferase 10 (NAT10) as a substrate for Khib modification. We further showed that Khib modification at lysine 823 in NAT10 functionally contribute to metastasis. Mechanistically, NAT10 Khib modification enhances its interaction with deubiquitinase USP39, resulting in increased NAT10 protein stability. NAT10 in turn promotes metastasis by increasing NOTCH3 mRNA stability in an N4-acetylcytidine-dependent manner. Furthermore, we discovered a lead compound #7586-3507 that inhibited NAT10 Khib modification and showed efficacy in tumor models in vivo at a low concentration. Together, our findings bridge newly identified lysine acylation modifications with RNA modifications, thus providing novel insights into epigenetic regulation in human cancer. We propose that pharmacological inhibition of NAT10 K823 Khib modification constitutes a potential anti-metastasis strategy., (© 2023. The Author(s) under exclusive licence to Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences.)

Human chorionic gonadotropin (hCG) might affect endometrial receptivity, exerting integral roles in embryo implantation. This study explored the action of hCG in endometrial receptivity via the miR-126-3p/PIK3R2/PI3K/Akt/eNOS axis. The embryo implantation dysfunction (EID) mouse models were established by administrating mifepristone and human endometrial epithelial cells (EECs) were used for in vivo experiments, both followed by hCG treatment. Expression level of CD105 and protein levels of cadherin CD144 and CD146 in mice were determined by immunohistochemistry and Western blot. The levels of miR-126-3p and PIK3R2 mRNA and PIK3R2, p-PI3K p85 α, PI3K p110 α, p-Akt, Akt, p-eNOS, and eNOS protein levels were measured. Cell proliferation was evaluated by CCK-8 and EdU assays. The binding sites of miR-126-3p and PIK3R2 were predicted and verified. hCG-treated EECs were further transfected with miR-126-inhibitor for functional rescue experiments. hCG ameliorated endometrial receptivity in EID mice. Moreover, hCG promoted miR-126-3p and suppressed PIK3R2 in EID mice and EECs. miR-126-3p targeted PIK3R2. EEC proliferation was enhanced after hCG treatment but inhibited by miR-126-3p downregulation. Both in vivo and in vitro experiments validated that hCG activated the PI3K/Akt/eNOS pathway through the miR-126-3p/PIK3R2 axis. Collectively, hCG improves endometrial receptivity by activating the PI3K/Akt/eNOS pathway via regulating miR-126-3p/PIK3R2., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR , 1.10, 95% CI , 1.01-1.21, P =0.029, CV: HR , 1.11, 95% CI , 1.02-1.21, P =0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% ( HR , 0.75; 95% CI , 0.65-0.87; P <0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted ( P ≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality ( HR , 0.68; 95% CI , 0.47-1.00; P =0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.

Establishing a stoke experimental model, which is better in line with the physiology and function of human brain, is the bottleneck for the development of effective anti-stroke drugs. A three-dimensional cerebral organoids (COs) from human pluripotent stem cells can mimic cell composition, cortical structure, brain neural connectivity and epigenetic genomics of in-vivo human brain, which provides a promising application in establishing humanized ischemic stroke model. COs have been used for modeling low oxygen condition-induced hypoxic injury, but there is no report on the changes of COs in response to in vitro oxygen-glucose deprivation (OGD)-induced damage of ischemic stroke as well as its application in testing anti-stroke drugs. In this study we compared the cell composition of COs at different culture time and explored the cell types, cell ratios and volume size of COs at 85 days (85 d-CO). The 85 d-CO with diameter more than 2 mm was chosen for establishing humanized ischemic stroke model of OGD. By determining the time-injury relationship of the model, we observed aggravated ischemic injury of COs with OGD exposure time, obtaining first-hand evidence for the damage degree of COs under different OGD condition. The sensitivity of the model to ischemic injury and related treatment was validated by the proven pan-Caspase inhibitor Z-VAD-FMK (20 μM) and Bcl-2 inhibitor navitoclax (0.5 μM). Neuroprotective agents edaravone, butylphthalide, P7C3-A20 and ZL006 (10 μM for each) exerted similar beneficial effects in this model. Taken together, this study establishes a humanized ischemic stroke model based on COs, and provides evidence as a new research platform for anti-stroke drug development., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To predict risk factors for Bakri balloon tamponade (BBT) failure in the management of postpartum hemorrhage (PPH)., Methods: The data of 599 patients who underwent BBT were retrospectively analyzed from January 1, 2017 to December 31, 2021 in a tertiary hospital in Shanghai, East China. The patients were divided into the failure group and the success group. Failure was defined as the inability to control bleeding, which required surgical interventions. Maternal characteristics, PPH characteristics, PPH management approaches, and maternal complications were compared between the groups. The independent predictors of BBT failure were analyzed by logistic regression analysis., Results: The overall success rate of BBT was 83.0% (497/599). The blood loss before and after balloon insertion in the failure group was significantly greater than that in the success group. Of the 102 failures, B-Lynch suture was performed in one patient, uterine artery embolization was performed in 99 patients (with one failure), and total hysterectomy was performed in three patients. Some risk factors, including twin gestation (odds ratio [OR] 9.68), placenta accreta spectrum with/without placenta previa (OR 4.45), estimated blood loss at least 1135 ml at balloon insertion (OR 3.35), multiparous (OR 2.72), and in vitro fertilization-embryo transfer (OR 2.00) were strongly associated with BBT failure., Conclusion: BBT seemed to be a less effective tool in the management of PPH due to placenta accreta spectrum with/without placenta previa and twin gestation., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: To establish better diagnosis thinking and provide advanced understanding of MSK, the CT imaging features, clinical characteristics, and the expression of suspected genes in the kidney spatiotemporal immune zonation and fetal renal development were investigated., Methods: 17 patients with MSK hospitalized in our hospital were selected as our research subjects. Human Phenotype Ontology, MalaCards: The Human Disease Database, GeneCards: The Human Gene Database, Human Protein Atlas, and Single Cell Expression Atlas were used to analyze this disease., Results: In our 17 patients, the incidence of MSK tended to be the same in male and female, and the onset age of MSK was probably 31-50 years old. The top one related disease of MSK was nephrocalcinosis and the most frequent phenotype related to MSK was nephrolithiasis. In addition, the expression of HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 has been implicated in both human kidney immune zonation and fetal kidney development., Conclusions: HNF1B, CLCN5, GDNF, ATP6V0A4, ATP6V1B1, LAMA2, RET, ACAN, and ABCC8 could be independent indicators for the diagnosis and preventive intervention of MSK patients, and abnormal kidney development due to mutations in key genes was the underlying cause of MSK., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Ming Li et al.)

Background: Post-traumatic hydrocephalus (PTH) is a complication of traumatic brain injury (TBI) that requires treatment and postoperative care. The shunt is one of the main treatments for PTH, which presents with dysfunction and infection. Considering brain injury, hydrocephalus shunt malfunction, and infection, family caregivers need to be responsible for caring for PTH patients, recognizing shunt malfunction and infection, and managing those patients accordingly from hospital to home. Understanding the experiences and needs of caregivers is beneficial for knowing their competency and quality of health care, ameliorating and ensuring future transition care. The study aimed to explore the feelings, experiences, and needs of family caregivers when caring for patients with TBI, PTH and shunts., Methods: This was exploratory research of a purposive sample of 12 family caregivers of adult patients with TBI, PTH and shunts in five neurosurgery departments at a general hospital in Zhengzhou, Henan Province, China, using a semi-structured interview method. Data were collected from October 2021 to March 2022 before being analyzed by content analysis methods., Results: Caregivers required professional and social knowledge and support in the areas of TBI, PTH and shunts, caregiving interventions, psychological care needs, and health insurance, just as caregivers do, but unlike other general caregivers, care for patients with TBI, PTH, and shunt is fraught with uncertainty and the need to manage shunt setting, and caregivers often experience 'complex emotional reaction' during the transitional period, where care needs and complex emotions may lead to a lack of caregiver confidence, which in turn may affect caregiving behaviors, and experiences that affect care may be mediated through caregiving confidence. The perceived availability of resources, particularly those that are still available to them when they return home, has a significant impact on participants' emotional response and sense of confidence., Conclusions: The emotional response and the impact of stressor caregivers after TBI, PTH, and shunt was important, and sometimes confidence in care appeared to be an intermediate and useful factor that needed to be considered as health professionals prepared to develop care resources on how to manage and empower patients with TBI, PTH, and shunt. Meanwhile, there may be gaps and inequities in supportive care for patients diagnosed with TBI, PTH, and shunt in China., (© 2022. The Author(s).)

There is emerging evidence that α1-blockers can be safely used in the treatment of hypertension. These drugs can be used in almost all hypertensive patients for blood pressure control. However, there are several special indications. Benign prostatic hyperplasia is a compelling indication of α1-blockers, because of the dual treatment effect on both high blood pressure and lower urinary tract symptoms. Many patients with resistant hypertension would require α1-blockers as add-on therapy. Primary aldosteronism screen is a rapidly increasing clinical demand in the management of hypertension, where α1-blockers are useful for blood pressure control in the preparation for the measurement of plasma aldosterone and renin. Nonetheless, α1-blockers have to be used under several considerations. Among the currently available agents, only long-acting α1-blockers, such as doxazosin gastrointestinal therapeutic system 4-8 mg daily and terazosin 2-4 mg daily, should be chosen. Orthostatic hypotension is a concern with the use of α1-blockers especially in the elderly, and requires careful initial bedtime dosing and avoiding overdosing. Fluid retention is potentially also a concern, which may be overcome by combining an α1-blocker with a diuretic., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: To uncover advanced prognosis biomarkers in patient with kidney renal clear cell carcinoma (KIRC), our study was the first to make a comprehensive analysis of hsa-mir-21 predicted target genes and explore the immune characteristics in KIRC. Methods: In this study, the comprehensive analysis of hsa-mir-21 predicted target genes and immune characteristics in KIRC were analyzed via TIMER2.0, UALCAN, Metascape, Kaplan-Meier plotter, Human Protein Atlas, CancerSEA, JASPAR, GEPIA, R package: GSVA package (version 1.34.0) & immune infiltration algorithm (ssGSEA) and R package: RMS package (version 6.2-0) & SURVIVAL package (version 3.2-10). Results: Up-transcriptional expressions of RP2, NFIA, SPRY1 were significantly associated with favorable prognosis in KIRC, whereas that of TGFBI was markedly significantly to unfavorable prognosis. Additionally, RP2, NFIA, SPRY1 and TGFBI were significantly relevant to the immune infiltration in KIRC. Finally, ZNF263 was a common predicted transcription factor of RP2, NFIA, SPRY1 and TGFBI, which can as an independent indicator for prognosis in KIRC patients. Conclusions: Hsa-mir-21 predicted target genes (RP2, NFIA, SPRY1 and TGFBI) and the common transcription factor ZNF263 could be the advanced prognosis biomarkers in KIRC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To uncover novel prognostic and therapeutic targets for BLCA, our study is the first to investigate the role of hsa-mir-183 and its up-regulated predicted target genes in bladder urothelial carcinoma., Methods: To address this issue, our study explored the roles of hsa-mir-183 predicted target genes in the prognosis of BLCA via UALCAN, Metascape, Kaplan-Meier plotter, Human Protein Atlas, TIMER2.0, cBioPortal and Genomics of Drug Sensitivity in Cancer databases., Results: High transcriptional expressions of PDCD6, GNG5, PHF6 and MAL2 were markedly relevant to favorable OS in BLCA patients, whereas SLC25A15 and PTDSS1 had opposite expression significance. Additionally, high transcriptional expression of PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 were significantly correlated with BLCA individual cancer stages and molecular subtypes. Furthermore, high mutation rate of PDCD6, MAL2, SLC25A15 and PTDSS1 were observed. Finally, TP53 mutation of PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 has guiding significance for drug selection in BLCA., Conclusions: PDCD6, GNG5, PHF6, MAL2, SLC25A15 and PTDSS1 could be the advanced independent indicators for prognosis of BLCA patients, and TP53-mutation might be a biomarker for drug option in BLCA patients.

Photomechanical molecular crystals are promising candidates for photoactuators and can potentially be implemented as smart materials in various fields. Here, we synthesized a new molecular crystal, ( E )-3-(naphthalen-1-yl)acrylaldehyde malononitrile (( E )- NAAM ), that can undergo a solid-state [2 + 2] photocycloaddition reaction under visible light (≥400 nm) illumination. ( E )- NAAM microcrystals containing symmetric twinned sealed cavities were prepared using a surfactant-mediated crystal seeded growth method. When exposed to light, the hollow microcrystals exhibited robust photomechanical motions, including bending and dramatic directional expansion of up to 43.1% elongation of the original crystal length before fragmentation due to the photosalient effect. The sealed cavities inside the microcrystals could store different aqueous dye solutions for approximately one month and release the solutions instantly upon light irradiation. A unique slow-fast-slow crystal elongation kinematic process was observed, suggesting significant molecular rearrangements during the illumination period, leading to an average anisotropic crystal elongation of 37.0% (±3.8%). The significant molecular structure and geometry changes accompanying the photocycloaddition reaction, which propels photochemistry to nearly 100% completion, also facilitate photomechanical crystal expansion. Our results provide a possible way to rationally design molecular structures and engineer crystal morphologies to promote more interesting photomechanical behaviors.

Background: Current guideline recommends both surgery and drug treatment for primary aldosteronism. Treatment effects on the cardiac structure and function remain under investigation., Objective: We performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocardial deformation and LV pressure., Methods: Our study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed conventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up., Results: During follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass index and left atrial volume index. However, only in the surgery group did global wasted work significantly decrease (200.8 ± 86.7 at baseline vs. 142.1 ± 58.1 mmHg% at 6 months) and global work efficiency (91.5 ± 3.1 vs . 93.6 ± 2.3%) and global longitudinal strain (-18.3 ± 2.7 vs . -19.2 ± 1.9%) significantly ( p < 0.01) increase at 6 months of follow-up. The corresponding differences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), -1.64% (95% CI, -2.56, -0.71%), and -0.85% (95% CI, -1.51, -0.20%), respectively. In addition, the changes in global wasted work at 6 months of follow-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group ( r = 0.54) and two groups combined ( r = 0.55), but not the surgery group., Conclusion: In spite of similar serum potassium normalization and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function., 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 Chen, Xu, Xu, Zhu, Li and Wang.)

We investigated the myocardial work derived from left ventricular pressure-strain loop in patients with primary aldosteronism or primary hypertension. We enrolled 50 patients with primary aldosteronism, 50 age- and sex-matched patients with primary hypertension, and 25 normotensive control subjects. We performed transthoracic echocardiography and speckle-tracking echocardiography-based left ventricular pressure-strain loop analysis to evaluate cardiac structure and function. Patients with primary aldosteronism and those with primary hypertension had similar clinic and ambulatory blood pressures, except that the former had a significantly (P = 0.03) higher nighttime systolic blood pressure. All subjects had normal left ventricular ejection fraction (66.4 ± 4.7%). Patients with primary aldosteronism had a greater left ventricular mass index than those with primary hypertension and the normal controls (111.0 ± 21.6 g/m 2 versus 95.7 ± 17.7 and 77.9 ± 13.5 g/m 2 , respectively, P < 0.001). The global myocardial work index (GWI, 2336 ± 333, 2366 ± 288, and 2292 ± 249 mmHg%, respectively), and global constructive work (GCW, 2494 ± 325, 2524 ± 301, and 2391 ± 193 mmHg%, respectively), were comparable in the three groups (P ≥ 0.18). However, the global work efficiency (GWE) differed significantly (P < 0.001), being lowest in primary aldosteronism (91.1 ± 2.7%), intermediate in primary hypertension (93.5 ± 2.5%) and highest in controls (95.3 ± 1.5%). The opposite was true for the global wasted work (GWW) (205.6 ± 74.6, 142.0 ± 56.4 and 99.4 ± 33.7 mmHg%, respectively, P < 0.001). GWE was significantly correlated with the logarithmically transformed plasma concentration and the urinary excretion of aldosterone in patients with primary aldosteronism or primary hypertension (r = -0.43 for both, P < 0.001). The associations remained statistically significant (P ≤ 0.04) after further adjustment for several factors, including left ventricular mass index and clinic or nighttime blood pressure. In conclusion, GWE decreased and GWW increased in primary hypertension and further in primary aldosteronism, probably because of the adrenal aldosterone hypersecretion and the left ventricular mass index increase, while GWI and GCW were similar, indicating that similar and normalized total myocardial work might be a compensation in hypertension at the expense of work efficiency., (© 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: The evaluation of the difficult intubation is an important process before anaesthesia. The unanticipated difficult intubation is associated with morbidity and mortality. This study aimed to determine whether acoustic features are valuable as an alternative method to predict difficult laryngoscopy (DL) in patients scheduled to undergo orthognathic surgery., Methods: This study included 225 adult patients who were undergoing elective orthognathic surgery under general anaesthesia with tracheal intubation. Preoperatively, clinical airway evaluation was performed, and the acoustic data were collected. Twelve phonemes {[a], [o], [e], [i], [u], [ü], [ci], [qi], [chi], [le], [ke], and [en]} were recorded, and their formants (f1-f4) and bandwidths (bw1-bw4) were extracted. Difficult laryngoscopy was defined as direct laryngoscopy with a Cormack-Lehane grade of 3 or 4. Univariate and multivariate logistic regression analyses were used to examine the associations between acoustic features and DL., Results: Difficult laryngoscopy was reported in 59/225 (26.2%) patients. The area under the curve (AUC) of the backward stepwise model including en&#95;f2 [odds ratio (OR), 0.996; 95% confidence interval (CI), 0.994-0.999; P=0.006], ci&#95;bw4 (OR, 0.997; 95% CI, 0.993-1.000; P=0.057), qi&#95;bw4 (OR, 0.996; 95% CI, 0.993-0.999; P=0.017), le&#95;f3 (OR, 0.998; 95% CI, 0.996-1.000; P=0.079), o&#95;bw4 (OR, 1.001; 95% CI, 1.000-1.003; P=0.014), chi&#95;f4 (OR, 1.003; 95% CI, 1.000-1.005; P=0.041), a&#95;bw4 (OR, 0.999; 95% CI, 0.998-1.000; P=0.078) attained a value of 0.761 in the training set, but a value of 0.709 in the testing set. The sensitivity and specificity of the model in the testing set are 86.7% and 63.0%, respectively., Conclusions: Acoustic features may be considered as useful predictors of DL during orthognathic surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4359). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Purpose: We investigated continuous positive airway pressure (CPAP) adherence and its association with the blood pressure (BP) and pulse rate changes in patients with obstructive sleep apnoea syndrome (OSAS) and hypertension., Materials and Methods: In a single-blind trial, patients were randomly assigned to CPAP or sham CPAP treatment for 3 months. We performed clinic, ambulatory and home BP measurements at baseline and during follow-up. CPAP adherence was assessed as the CPAP frequency per week and time per night. Non-adherence was defined as a CPAP use for <5 days/week or <4 h/night., Results: In the CPAP ( n  = 26) and sham CPAP groups ( n  = 21), the CPAP frequency was 5.5 and 4.8 days/week ( p  = 0.17), respectively, and the CPAP time was 5.0 and 4.1 h/night ( p  = 0.03), respectively. The corresponding prevalence of non-adherence was 46.2% and 66.7% ( p  = 0.16), respectively. The CPAP frequency but not time tended to be associated with the changes in BP and pulse rate at 3 months of follow-up, especially home systolic/diastolic BP in the CPAP group (3.2/1.3 mmHg greater reductions per 1 day increment, p  ≤ 0.01). Adherent, compared with non-adherent patients, had greater reductions in BP or pulse rate at 3 months of follow-up. In the CPAP and sham CPAP groups combined, statistical significance was achieved for the adjusted between adherence and non-adherence differences in home systolic/diastolic BP (-5.0/-3.8 mmHg) and 24-h, daytime and night-time ambulatory pulse rate (-6.2, -7.8 and -4.4 beats/min, respectively, p  ≤ 0.04)., Conclusion: CPAP adherence was associated with the BP lowering and pulse rate slowing effects, especially the CPAP frequency.

Designing photo-responsive host-guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo-responsive macrocyclic hosts, modulated by light-driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first-generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown-ether-like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host-guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi-state light-driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli-responsive host-guest systems and dynamic materials., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Doxorubicin is one of the most frequently used chemotherapy drugs in the treatment of osteosarcoma (OS), but the emergence of chemoresistance often leads to treatment failure. C‑X‑C motif chemokine receptor 4 (CXCR4) has been demonstrated to regulate OS progression and metastasis. However, whether CXCR4 is also involved in OS chemoresistance and its molecular mechanisms has yet to be fully elucidated. In the present study, CXCR4‑mediated autophagy for OS chemotherapy was investigated by western blot analysis, transmission electron microscopy and confocal microscopy. CXCR4 silencing enhanced doxorubicin‑induced apoptosis by reducing P‑glycoprotein in CXCR4 + LM8 cells, while CXCR4 overexpression promoted OS doxorubicin resistance in CXCR4 ‑ Dunn cells. Furthermore, CXCR4 silencing with or without doxorubicin increased the expression of beclin 1 and light chain 3B, and the number of autophagosomes and autolysosomes, as well as induced autophagic flux activation by suppressing the PI3K/AKT/mTOR signaling pathway. In addition, pretreatment with the autophagy inhibitor bafilomycin A1 attenuated CXCR4 abrogation‑induced cell death. Finally, the CXCR4 antagonist AMD3100 synergistically reinforced the antitumor effect of doxorubicin in an orthotopic OS mouse model. Taken together, the present study revealed that CXCR4 inhibition sensitizes OS to doxorubicin by inducing autophagic cell death. Therefore, targeting the CXCR4/autophagy axis may be a promising therapeutic strategy to overcome OS chemotherapy resistance.

Hypertension is a serious public health problem worldwide. MT-1207, chemically named 3-(4-(4-(1H-benzotriazole-1-yl)butyl)piperazine-1-yl) benzisothiazole hydrochloride, is a new chemical entity that has entered into clinical trial as antihypertensive agent in China. In this paper we report the pharmacological profile of MT-1207 regarding its acute, subacute, and long-term effects on hypertensive animal models, and its actions on isolated organs in vitro as well as its molecular targets. Blood pressure (BP) was measured in conscious animals; amlodipine was taken as a positive control drug. We showed that both single dose of MT-1207 (1.25-20 mg/kg, ig) in spontaneously hypertensive rats (SHR) and MT-1207 (0.25-6 mg/kg, ig) in two-kidney one-clip (2K1C) dogs dose-dependently decreased BP. MT-1207 quickly decreased BP within 5 min after administration; the hypotensive effect lasted for 8 and 12 h, respectively, in SHR and 2K1C dogs without reflex increase in heart rate. Multiple doses of MT-1207 (5 mg · kg -1  · d -1 in SHR; 2 mg · kg -1  · d -1 in 2K1C dogs, for 7 days) significantly decreased BP, slightly reduced heart rate, and both of them recovered after withdrawal. Long-term administration of MT-1207 (10 mg · kg -1  · d -1 for 4 months or more time) produced a stable BP reduction, improved baroreflex sensitivity, reduced renal and cardiovascular damage in SHR, and delayed stroke occurrence and death in stroke-prone SHR. In isolated rat aortic rings precontracted by adrenaline, KCl, noradrenaline or 5-hydroxytryptamine (5-HT), MT-1207 (10 -9 -10 -4  M) caused concentration-dependent relaxation. In a panel of enzyme activity or radioligand binding assays of 87 molecular targets, MT-1207 potently inhibited adrenergic α 1A , α 1B , α 1D , and 5-HT 2A receptors with K i  < 1 nM. The antagonism of MT-1207 against these receptors was confirmed in isolated rabbit arteries. We conclude that MT-1207 is a novel and promising single-molecule multitarget agent for hypertension treatment to reduce hypertensive organ damage and stroke mortality.

Nowadays, although the exploration of proton conductive materials has ranged from traditional sulfonated polymers to novel crystalline solid materials such as MOFs, COFs, and HOFs, research on crystalline cluster-based organic framework materials is very limited. Here, a pair of homologues Cu(i)-based organic framework containing a Cu12S6 cluster, [Cu12(MES)6(H2O)3]n (1) and {[Cu12(MPS)6(H2O)4]·6H2O}n (2) (H2MES = 2-mercaptoethanesulfonate acid and H2MPS = 2-mercaptoethanesulfonate acid), were hydrothermally synthesized under the same conditions and fully investigated for their proton conduction. Their structures were characterized by means of single-crystal X-ray diffraction, elemental analysis, thermogravimetric analyses, and PXRD measurements. The two MOFs show significant structural differences in the topological fashions. MOF 1 has a three-dimensional network and can be simplified into two topology types: a 10-connected gpu structure with a Schläfli symbol (312·426·57) and a 3,12-connected new topology with a point symbol {3·42}2{310·418·519·614·74·9}. MOF 2 also has a three-dimensional framework and topology as a 6-connected pcu primitive cubic network with a Schläfli symbol {412·63}. The two MOFs show different proton conduction parameters, but both indicate temperature-dependent proton conductive features. Intriguingly, the two MOFs exhibit high water stability and their proton conductivities are 3.63 × 10-5 and 2.75 × 10-5 S cm-1 under 333 K and 98% RH, respectively. The suggested mechanism for the synthesis for 1 and 2, and their proton conductivity performance comparison has been discussed in detail. In addition, Hirshfeld surface and fingerprint analysis on the two MOFs were computed to compare contacts between the molecules, which is essential for analyzing the relationships between their hydrogen bonds and proton conductivity properties.

Background: We investigated proximal and distal renal tubular sodium handling, as assessed by fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa), in relation to environmental and genetic factors in untreated patients., Methods: Our study participants were suspected hypertensive patients being off antihypertensive medication for ≥2 weeks and referred for 24-hour ambulatory blood pressure monitoring. We collected serum and 24-hour urine for measurement of sodium, creatinine, and lithium concentration, and calculated FELi and FDRNa. We genotyped 19 single-nucleotide polymorphisms associated with renal sodium handling or blood pressure using the ABI SNapShot method., Results: The 1,409 participants (664 men, 47.1%) had a mean (±SD) age of 51.0 ± 10.5 years. After adjustment for host factors, both FELi and FDRNa were significantly (P ≤ 0.01) associated with season and humidity, explaining ~1.3% and ~3.5% of the variance, respectively. FELi was highest in autumn and lowest in summer and intermediate in spring and winter (P = 0.007). FDRNa was also highest in autumn but lowest in winter and intermediate in spring and summer (P < 0.001). Neither FELi nor FDRNa was associated with outdoor temperature or atmospheric pressure (P ≥ 0.13). After adjustment for host and environmental factors and Bonferroni multiple testing, among the 19 studied genetic variants, only rs12513375 was significantly associated with FELi and FDRNa (P ≤ 0.004) and explained about 1.7% of the variance., Conclusions: Renal sodium handling as measured by endogenous lithium clearance was sensitive to major environmental and genetic factors. Our finding is toward the use of these indexes for the definition of renal tubular dysfunction., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: We investigated right ventricular function using speckle tracking echocardiography (STE) in patients with primary aldosteronism., Methods: Our study included 51 primary aldosteronism patients and 50 age and sex-matched primary hypertensive patients. We performed two-dimensional echocardiography to measure cardiac structure and function. We performed STE offline analysis on right ventricular four-chamber (RV4CLS) and free wall longitudinal strains (RVFWLS)., Results: Primary aldosteronism patients, compared with primary hypertensive patients, had a significantly (P ≤ 0.045) greater left ventricular mass index (112.0 ± 22.6 vs. 95.8 ± 18.5 g/m) and left atrial volume index (26.9 ± 6.0 vs. 24.7 ± 5.6 ml/m) and higher prevalence of left ventricular concentric hypertrophy (35.3 vs. 12.0%), although they had similarly normal left ventricular ejection fraction (55-77%). Primary aldosteronism patients also had a significantly (P ≤ 0.047) larger right atrium and ventricle, lower tricuspid annular plane systolic excursion, and higher E/E't (the peak early filling velocity of trans-tricuspid flow to the peak early filling velocity of lateral tricuspid annulus ratio), estimated pulmonary arterial systolic pressure and right ventricular index of myocardial performance. On the right ventricular strain analysis, primary aldosteronism patients had a significantly (P < 0.001) lower RV4CLS (-18.1 ± 2.5 vs. -23.3 ± 3.4%) and RVFWLS (-21.7 ± 3.7 vs. -27.9 ± 4.5%) than primary hypertensive patients. Overall, RV4CLS and RVFWLS were significantly (r = -0.58 to -0.41, P < 0.001) correlated with plasma aldosterone concentration and 24-h urinary aldosterone excretion. After adjustment for confounding factors, the associations for RV4CLS and RVFWLS with 24-h urinary aldosterone excretion remained significant (P < 0.001), with a standardized coefficient of -0.48 and -0.55, respectively., Conclusion: In addition to left ventricular abnormalities, primary aldosteronism patients also show impaired right ventricular function, probably because of hyperaldosteronism.

Background: To delineate the clinical characteristics associated with long-term viral shedding (>21 days) in patients with coronavirus disease 2019 (COVID-19)., Methods: In this retrospective study, factors associated with long-term (>21 days) severe acute respiratory coronavirus 2 (SARS-CoV-2) RNA shedding were evaluated in a conhort of 609 patients from two hospitals in Wuhan., Results: The median duration of SARS-CoV-2 viral shedding was 19 days (interquartile range, 10-28 days) among all patients. There were 42% of patients having prolonged viral shedding time (>21 days), in which the longest viral shedding time was 58 days. When comparing patients with early (≤21 days) and late viral RNA clearance (>21 days), prolonged viral shedding was associated with age <65 (P=0.015), female sex (P=0.028), cough (P=0.025), fatigue (P=0.035), sore throat (P=0.013), aspartate aminotransferase (P=0.038), procalcitonin (P=0.010), albumin (P=0.003), D-dimer (P=0.011), lung involvement (P=0.014), reticular shadow (P<0.001) and lung consolidation (P=0.004). Age range (<65 years) (odds ratio [OR], 1.46 [95% CI, 1.05-2.03]) and female sex (odds ratio [OR], 1.40 [95% CI, 1.00-1.94]) were independent risk factors., Conclusions: Long-term viral shedding (>21 days) is not a rare phenomenon among COVID-19 infectious patients. Age range (<65) and female sex are independent risk factors for long-term viral shedding. Early antiviral treatment should be considered for COVID-19 patients with such risk factors. Further study should be conducted to know the infectivity of patients with long-term viral shedding in order to develop reasonable control measures., Competing Interests: None., (AJTR Copyright © 2020.)

Stroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55 days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volume and improves neurological motor function. Transplanted COs show the potential of multilineage differentiation to mimic in vivo cortical development, support motor cortex region-specific reconstruction, form neurotransmitter-related neurons, and achieve synaptic connection with host brain via in situ differentiation and cell replacement in stroke. Cells from transplanted COs show extensive migration into different brain regions along corpus callosum. The mechanisms underlying COs transplantation therapy are also associated with enhanced neurogenesis, synaptic reconstruction, axonal regeneration and angiogenesis, and decreased neural apoptosis with more survival neurons after stroke. Moreover, COs transplantation promotes predominantly exogenous neurogenesis in the transplantation periphery of ipsilateral cortex and predominantly endogenous neurogenesis in the hippocampus and subventricular zone. Together, we demonstrate the efficacy and underlying mechanisms of COs transplantation in stroke. This preliminary but promising study provides first-hand preclinical evidence for COs transplantation as a potential and effective intervention for stroke treatment.

Purpose: Masked hypertension (MHT) is characterised as an office normotension in the presence of out-of-office hypertension, and can be further categorised as isolated daytime (dMHT), night-time (nMHT) or day-night MHT (dnMHT) according to the time when hypertension is present. MHT is associated with adverse cardiovascular outcome. However, no previous studies contrasted these MHT subtypes in their associations with target organ damage (TOD). Materials and methods: Consecutive untreated patients referred for ambulatory blood pressure (BP) monitoring to our Hypertension Clinic were recruited. Office and ambulatory BPs were measured using the Omron 7051 and SpaceLabs 90217 monitors, respectively. The BP thresholds of daytime and night-time hypertension were of ≥135/85 mmHg and ≥120/70 mmHg, respectively. We performed various TOD measurements, including carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI) and E/E', estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). Results: The 1808 participants (mean age, 51 years; women, 52%) included 672 (37.2%) MHT subjects, among whom 123 (18.3%) had dMHT, 78 (11.6%) nMHT, and 471 (70.1%) dnMHT. In all participants as well as patients with office normotension ( n  = 1222), ambulatory daytime and night-time BPs were similarly associated with all TOD measurements ( p  ≥ 0.20) after multivariate adjustment. Compared to normotensive subjects ( p  < 0.05), patients with dMHT had faster cfPWV (7.81 vs. 7.58 m/s) and thicker cIMT (637.6 vs. 610.4 µm), patients with nMHT had thicker cIMT (641.8 vs. 610.4 µm) and increased UACR (0.79 vs. 0.59 mg/mmol), and patients with dnMHT had all worse TOD measures mentioned-above plus elevated eGFR (120.7 vs. 116.8 ml/min/1.73m 2 ). Conclusion: MHT was associated with TOD irrespective of subtype, although TOD varied slightly across these subtypes. The study highlights the importance of controlling both daytime and night-time BP in hypertensive patients.

A pair of homologues, [Zn(Hssa)(1,4-bib)·H2O]n (1) and [Zn3(ssa)2(1,4-bib)3·4H2O]n (2), were successfully assembled using the same metals and ligands [H3ssa = 5-sulfosalicylic acid; 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene] under solvothermal conditions. Polymer 1 is a two-dimensional (2D) sql network and polymer 2 is a three-dimensional (3D) framework. Polymer 2 can be simplified into two topology types: bct and tfc. The two polymers show significant differences in the fluorescence sensing of metal ions and proton conductivity. Their applications in detecting metal ions and proton conductivity were explored. Polymer 1 shows high sensitivity and selectivity for Fe3+, while polymer 2 can detect Hg2+ ions. The limit of detection was 1.66 μM with Fe3+ for 1 and 0.23 μM with Hg2+ for 2 in water. In addition, both 1 and 2 exhibit high water stability and proton conductivity. At 60 °C and 95% relative humidity, their conductivities were 3.45 × 10-5 and 6.26 × 10-6 S cm-1, respectively. A detailed analysis of the Hirshfeld surface and fingerprints was carried out for 1 and 2 to compare the interactions between the molecules, which is essential for analysing the relationship between their structures and material properties.

Background and Purpose: Cerebral organoids (COs) have been used for studying brain development, neural disorders, and species-specific drug pharmacology and toxicology, but the potential of COs transplantation therapy for brain injury remains to be answered., Methods: With preparation of traumatic brain injury (TBI) model of motor dysfunction, COs at 55 and 85 days (55 and 85 d-CO) were transplanted into damaged motor cortex separately to identify better transplantation donor for brain injury. Further, the feasibility, effectiveness, and underlying mechanism of COs transplantation therapy for brain injury were explored., Results: 55 d-CO was demonstrated as better transplantation donor than 85 d-CO, evidenced by more neurogenesis and higher cell survival rate without aggravating apoptosis and inflammation after transplantation into damaged motor cortex. Cells from transplanted COs had the potential of multilinage differentiation to mimic in-vivo brain cortical development, support region-specific reconstruction of damaged motor cortex, form neurotransmitter-related neurons, and migrate into different brain regions along corpus callosum. Moreover, COs transplantation upregulated hippocampal neural connection proteins and neurotrophic factors. Notably, COs transplantation improved neurological motor function and reduced brain damage., Conclusions: This study revealed 55 d-CO as better transplantation donor and demonstrated the feasibility and efficacy of COs transplantation in TBI, hoping to provide first-hand preclinical evidence of COs transplantation for brain injury., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)