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Huntington disease (HD) is a single-gene autosomal dominant inherited neurodegenerative disease caused by a polyglutamine expansion of the protein huntingtin (HTT). Huntingtin-associated protein 1 (HAP1) is the first protein identified as an interacting partner of huntingtin, which is directly associated with HD. HAP1 is mainly expressed in the nervous system and is also found in the endocrine system and digestive system, and then involves in the occurrence of the related endocrine diseases, digestive system diseases, and cancer. Understanding the function of HAP1 could help elucidate the pathogenesis that HTT plays in the disease process. Therefore, this article attempts to summarize the latest research progress of the role of HAP1 and its application for diseases in recent years, aiming to clarify the functions of HAP1 and its interacting proteins, and provide new research ideas and new therapeutic targets for the treatment of cancer and related diseases., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

A visible-light-mediated late-stage sulfonylation of anilines with sulfonamides under simple reaction conditions is presented. Various primary or secondary sulfonamides including several pharmaceuticals were incorporated successfully via N-S bond activation and C-H bond sulfonylation. The synthetic utility of this strategy is highlighted by the construction of complex anilines bearing diverse bioactive groups.

The first C-H trifluoroethylamination of heteroarenes with previously unknown N -trifluoroethyl hydroxylamine reagents was achieved under photoredox catalyzed conditions. In the presence of an iridium(III) photoredox catalyst, a variety of heteroarenes, such as indoles, benzofurans, and benzothiophenes, were smoothly converted to the trifluoroethylaminated products in moderate to high yields and with excellent regioselectivity.

Trifluoromethoxylated aromatics (ArOCF 3 ) are valuable structural motifs in the area of drug discovery due to the enhancement of their desired physicochemical properties upon the introduction of the trifluoromethoxy group (CF 3 O). Although significant progress has been made recently in the introduction of CF 3 O group into aromatics, current methods either require the use of expensive trifluoromethoxylation reagents or require harsh reaction conditions. We present a conceptually new and operationally simple protocol for the direct C-H trifluoromethoxylation of (hetero)aromatics by the combination of the readily available trifluoromethylating reagent and oxygen under electrochemical reaction conditions. This reaction proceeds through the initial generation of CF 3 radical followed by conversion to CF 3 O radical, addition to (hetero)aromatics and rearomatization. The utility of this electrochemical trifluoromethoxylation is illustrated by the direct incorporation of CF 3 O group into a variety of (hetero)aromatics as well as bio-relevant molecules., (© 2021 Wiley-VCH GmbH.)

Purpose: Due to age and gender, patients awaiting total knee or hip arthroplasty (TKA/THA) are at a higher risk of osteoporosis. In joint arthroplasty, low bone mineral density (BMD) is a risk factor for implant osseointegration, durability, and prosthesis complications. This study aims to investigate the prevalence and treatment rate of osteoporosis in patients undergoing total joint arthroplasty (TJA)., Methods: We applied a comprehensive literature search through PubMed, Cochrane Library, and EMBASE from inception to July 10, 2021, for studies investigating the prevalence and treatment rate of osteoporosis in TJA patients. The aggregated prevalence was calculated with the random-effects model, and the heterogeneity between studies was checked by Cochran's Q test and quantified by the I 2 statistic. We performed subgroup analyses and meta-regression analyses to determine the source of heterogeneity. Publication bias was assessed by a funnel plot and verified by Egger's test. Anti-osteoporosis treatment for TJA patients was described qualitatively and quantitatively., Results: Of 4561 citations identified by the search strategy, 11 studies including 3462 patients were eligible for inclusion. The pooled prevalence of osteoporosis and osteopenia in TJA patients was 24.8% (95%CI: 14.1-37.2%) and 38.5% (95%CI: 29.3-48.0%), respectively. The prevalence of osteoporosis/osteopenia in TJA patients was 64.0% (95%CI: 45.8-80.3%). In terms of gender, the pooled prevalence of osteoporosis in males, females, and postmenopausal females were 5.5% (95%CI: 1.5-11.4%), 29.0% (95%CI: 18.3-41.1%), and 38.3% (95%CI: 13.2-67.1%), respectively. The treatment rate of osteoporosis in TJA patients was 32.9% (95%CI: 15.2-53.1%) by a random-effects model., Conclusions: Osteoporosis is highly prevalent in patients undergoing TJA, especially in postmenopausal females. However, the treatment rate of osteoporosis is low. Considering the possibility of surgical complications, clinicians should strengthen their awareness of pre-operative BMD assessment and manage osteoporosis in high-risk patients., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Porous materials have recently attracted much attention owing to their fascinating structures and broad applications. Moreover, exploring novel porous polymers affording the efficient capture of iodine is of significant interest. In contrast to the reported porous polymers fabricated with small molecular blocks, we herein report the preparation of porous polymer frameworks using rigid polyisocyanides as building blocks. First, tetrahedral four-arm star polyisocyanides with predictable molecular weight and low dispersity were synthesized; the chain-ends of the rigid polyisocyanide blocks were then crosslinked, yielding well-defined porous organic frameworks with a designed pore size and narrow distribution. Polymers of appropriate pore size were observed to efficiently capture radioactive iodine in both aqueous and vapor phases. More than 98% of iodine could be captured within 1 minute from a saturated aqueous solution (capacity of up to 3.2 g g -1 ), and an adsorption capacity of up to 574 wt% of iodine in vapor was measured within 4 hours. Moreover, the polymers could be recovered and recycled for iodine capture for at least six times, while maintaining high performance., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Coronavirus disease 2019 (COVID-19) broke out in December 2019. Due its high morbility and mortality, it is necessary to summarize the clinical characteristics of COVID-19 patients to provide more theoretical basis for future treatment. In the current study, we conducted a retrospective analysis of the clinical characteristics of COVID-19 patients and explored the risk factors for the severity of illness. A total of 101 COVID-19 patients hospitalized in Leishenshan Hospital (Wuhan, China) was classified into three sub-types: moderate (n = 47), severe (n = 36), and critical (n = 18); their clinical data were collected from the Electronic Medical Record. We showed that among the 101 COVID-19 patients, the median age was 62 years (IQR 51-74); 50 (49.5%) patients were accompanied by hypertension, while 25 (24.8%) and 22 (21.8%) patients suffered from diabetes and heart diseases, respectively, with complications. All patients were from Wuhan who had a definite history of exposure to the epidemic area. Multivariate logistic regression analysis revealed that older age, diabetes, chronic liver disease, percentage of neutrophils (N%) > 75%, CRP > 4 mg/L, D-dimer > 0.55 mg/L, IL-2R > 710 U/mL, IL-8 > 62 pg/mL, and IL-10 > 9.1 pg/mL were independent variables associated with severe COVID-19. In conclusion, we have identified the independent risk factors for the severity of COVID-19 pneumonia, including older age, diabetes, chronic liver disease, higher levels of N%, CRP, D-dimer, IL-2R, IL-8, and IL-10, providing evidence for more accurate risk prediction., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Background: As one of the effective pharmacological constituents of Ginseng Radix et Rhizoma, ginsenoside Rh2 (Rh2) exerts a remarkable anticancer effect on various cancer cell lines in vitro and strongly inhibits tumor growth in vivo without severe toxicity., Objective: This article reviewed existing evidence supporting the anticancer effects of Rh2 to classify and conclude previous and current knowledge on the mechanisms and therapeutic effects of Rh2, as well as to promote the clinical application of this natural product., Conclusion: This article reviewed the anticancer efficacies and mechanisms of Rh2, including the induction of cell cycle arrest and programmed cell death, repression of metastasis, alleviation of drug resistance, and regulation of the immune system. Finally, this paper discussed the research and application prospects of Rh2., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Androgen receptor (AR), a ligand-activated transcription factor, is a master regulator in the development and progress of prostate cancer (PCa). A major challenge for the clinically used AR antagonists is the rapid emergence of resistance induced by the mutations at AR ligand binding domain (LBD), and therefore the discovery of novel anti-AR therapeutics that can combat mutation-induced resistance is quite demanding. Therein, blocking the interaction between AR and DNA represents an innovative strategy. However, the hits confirmed targeting on it so far are all structurally based on a sole chemical scaffold. In this study, an integrated docking-based virtual screening (VS) strategy based on the crystal structure of the DNA binding domain (DBD) of AR was conducted to search for novel AR antagonists with new scaffolds and 2-(2-butyl-1,3-dioxoisoindoline-5-carboxamido)-4,5-dimethoxybenzoicacid (Cpd39) was identified as a potential hit, which was competent to block the binding of AR DBD to DNA and showed decent potency against AR transcriptional activity. Furthermore, Cpd39 was safe and capable of effectively inhibiting the proliferation of PCa cell lines (i.e., LNCaP, PC3, DU145, and 22RV1) and reducing the expression of the genes regulated by not only the full-length AR but also the splice variant AR-V7. The novel AR DBD-ARE blocker Cpd39 could serve as a starting point for the development of new therapeutics for castration-resistant PCa., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

The prevalence of Helicobacter pylori infection is high worldwide, while numerous research has focused on unraveling the relationship between H. pylori infection and extragastric diseases. Although H. pylori infection has been associated with thyroid diseases, including thyroid nodule (TN), the relationship has mainly focused on potential physiological mechanisms and has not been validated by large population epidemiological investigations. Therefore, we thus designed a case-control study comprising participants who received regular health examination between 2017 and 2019. The cases and controls were diagnosed via ultrasound, while TN types were classified according to the guidelines of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). Moreover, H. pylori infection was determined by C14 urea breath test, while its relationship with TN type risk and severity was analyzed using binary and ordinal logistic regression analyses. A total of 43,411 participants, including 13,036 TN patients and 30,375 controls, were finally recruited in the study. The crude odds ratio (OR) was 1.07 in Model 1 (95% CI = 1.03-1.14) without adjustment compared to the H. pylori non-infection group. However, it was negative in Model 2 (OR = 1.02, 95% CI = 0.97-1.06) after being adjusted for gender, age, body mass index (BMI), and blood pressure and in Model 3 (OR = 1.01, 95% CI = 0.97-1.06) after being adjusted for total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein on the basis of Model 2. Control variables, including gender, age, BMI, and diastolic pressure, were significantly correlated with the risk of TN types. Additionally, ordinal logistic regression results revealed that H. pylori infection was positively correlated with malignant differentiation of TN (Model 1: OR = 1.06, 95% CI = 1.02-1.11), while Model 2 and Model 3 showed negative results (Model 2: OR = 1.01, 95% CI = 0.96-1.06; Model 3: OR = 1.01, 95% CI = 0.96-1.05). In conclusion, H. pylori infection was not significantly associated with both TN type risk and severity of its malignant differentiation. These findings provide relevant insights for correcting possible misconceptions regarding TN type pathogenesis and will help guide optimization of therapeutic strategies for thyroid diseases., 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 Wang, Xu, Jiang, Ling, Ye, Zhao, Li, Lei, Hu, Chen and Wang.)

Accurate control of the layer number of orderly stacked 2D polymers has been an unsettled challenge in self-assembly. Herein we describe the fabrication of a bilayer 2D supramolecular organic framework from a monolayer 2D supramolecular organic framework in water by utilizing the cooperative coordination of a rod-like bipyridine ligands to zinc porphyrin subunits of the monolayer network. The monolayer supramolecular framework is prepared from the co-assembly of an octacationic zinc porphyrin monomer and cucurbit[8]uril (CB[8]) in water through CB[8]-encapsulation-promoted dimerization of 4-phenylpyridiunium subunits that the zinc porphyrin monomer bear. The bilayer 2D supramolecular organic framework exhibits structural regularity in both solution and the solid state, which is characterized by synchrotron small-angle X-ray scattering and high-resolution transmission electron microscopic techniques. Atomic force microscopic imaging confirms that the bilayer character of the 2D supramolecular organic framework can be realized selectively on the micrometer scale., (© 2021 Wiley-VCH GmbH.)

Background: Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4) are used to diagnose thyroid diseases and monitor treatment effects. Reliable biological variation (BV) data is required to ensure accurate clinical decisions., Methods: Blood samples were collected from 31 healthy subjects at 00:00, 04:00, 08:00, 12:00, 16:00, and 20:00; each sample was analyzed twice for TSH, T3, T4, FT3, and FT4. After outlier exclusion, normality assessment, and variance homogeneity, sex-stratified BV, including within-subject (CV I ) and between-subject (CV G ), was defined using nested ANOVA., Results: Concentrations of five biomarkers were significantly different between sexes. The CV I and CV G estimates were 34.54% and 34.43% for TSH, 5.89% and 14.18% for T3, 4.48% and 14.96% for T4, 5.37% and 11.23% for FT3, and 3.57% and 8.03% for FT4, respectively. The individual indexes (IIs) of all the biomarkers (except TSH) were ≤ 0.63. Males had lower CV I s and IIs than females., Conclusion: CV I estimates of all hormones, except TSH, were lower than those reported on the BV website, showing low IIs and differences between sexes. We provide updated data on the short-term BV of thyroid function biomarkers according to sex and complement BV data of thyroid function biomarkers., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Individuals of many species fight with conspecifics to gain access to or defend critical resources essential for survival and reproduction. Such intraspecific fighting is evolutionarily selected for in a species-, sex-, and environment-dependent manner when the value of resources secured exceeds the cost of fighting. One such example is males fighting for chances to mate with females. Recent advances in new tools open up ways to dissect the detailed neural circuit mechanisms that govern intraspecific, particularly inter-male, aggression in the model organism Mus musculus (house mouse). By targeting and functional manipulating genetically defined populations of neurons and their projections, these studies reveal a core neural circuit that controls the display of reactive male-male attacks in mice, from sensory detection to decision making and action selection. Here, we summarize these critical results. We then describe various modulatory inputs that route into the core circuit to afford state-dependent and top-down modulation of inter-male attacks. While reviewing these exciting developments, we note that how the inter-male attack circuit converges or diverges with neural circuits that mediate other forms of social interactions remain not fully understood. Finally, we emphasize the importance of combining circuit, pharmacological, and genetic analysis when studying the neural control of aggression in the future., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Study Question: Is the protein l-arginine methyltransferase 3 (PRMT3)/asymmetrical dimethylarginine (ADMA)/nitric oxide (NO) pathway involved in the development of recurrent miscarriage (RM), and what is the potential mechanism?, Summary Answer: Elevated levels of PRMT3 and ADMA inhibit NO formation in the decidua, thereby impairing the functions of trophoblast cells at the maternal-foetal interface., What Is Known Already: Decreased NO bioavailability is associated with RM. ADMA, an endogenous inhibitor of nitric oxide synthase (NOS), is derived from the methylation of protein arginine residues by PRMTs and serves as a predictor of mortality in critical illness., Study Design, Size, Duration: A total of 145 women with RM and 149 healthy women undergoing elective termination of an early normal pregnancy were enrolled. Ninety-six female CBA/J, 24 male DBA/2 and 24 male BALB/c mice were included. CBA/J × DBA/2 matings represent the abortion group, while CBA/J × BALB/c matings represent the normal control group. The CBA/J pregnant mice were then categorised into four groups: (i) normal + vehicle group (n = 28), (ii) abortion + vehicle group (n = 28), (iii) normal + SGC707 (a PRMT3 inhibitor) group (n = 20) and (iv) abortion + SGC707 group (n = 20). All injections were made intraperitoneally on Days 0.5, 3.5 and 6.5 of pregnancy. Decidual tissues were collected on Days 8.5, 9.5 and 10.5 of gestation. The embryo resorption rates were calculated on Day 9.5 and Day 10.5 of gestation., Participants/materials, Setting, Methods: NO concentration, ADMA content, NOS activity, expression levels of NOS and PRMTs in decidual tissues were determined using conventional assay kits or western blotting. PRMT3 expression was further analysed in decidual stromal cells, macrophages and natural killer cells. A co-culture system between decidual macrophages (DMs) and HTR-8/SVneo trophoblasts was constructed to study the roles of the PRMT3/ADMA/NO signalling pathway. Trophoblast apoptosis was analysed via Annexin V-fluorescein isothiocyanate/propidium iodide staining. CBA/J × DBA/2 mouse models were used to investigate the effects of SGC707 on embryo resorption rates., Main Results and the Role of Chance: Our results show that NO concentration and NOS activity were decreased, but ADMA content and PRMT3 expression were increased in the decidua of RM patients. Moreover, compared with the normal control subjects, PRMT3 expression was significantly up-regulated in the macrophages but not in the natural killer cells or stromal cells of the decidua from RM patients. The inhibition of PRMT3 results in a significant decrease in ADMA accumulation and an increase in NO concentration in macrophages. When co-cultured with DMs, which were treated with SGC707 and ADMA, trophoblast apoptosis was suppressed and induced, respectively. In vivo experiments revealed that the administration of SGC707 reduced the embryo resorption rate of CBA/J × DBA/2 mice., Limitations, Reasons for Caution: All sets of experiments were not performed with the same samples. The main reason is that each tissue needs to be reserved for clinical diagnosis and only a small piece of each tissue can be cut and collected for this study., Wider Implications of the Findings: Our results indicate that the PRMT3/ADMA/NO pathway is a potential marker and target for the clinical diagnosis and therapy of RM., Study Funding/competing Interest(s): This study was supported by the National Key Research and Development Program of China (2017YFC1001401), National Natural Science Foundation of China (81730039, 82071653, 81671460, 81971384 and 82171657) and Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015). The authors have declared no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future., 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 Zhu, Ma, Yu, Ouyang, Luo, Pei, Xu, Hu, Mo, Xu, Lan, Shen, Shou, Qian, Feng, Zhao, Jiang, Hu, Zhang, Qian, Wu, Wu, Qiu, Li, Lang, Chen, Chen, Guo, Cao, Jiang, Xia, Le, Zhao, Huang, Zhang, Lv, Hua, Hong, Zheng, Wang, Hu, Chen, Zhang, Tao, Xie, Kuang, Luo, Su, Guo, Wu, Jiang, Zhang, Zhang, Chen, Xu, Guo, Tu, Hu, Yan, Yao, Lou, Jin and the APL Cooperative Group of Zhejiang Province.)

Background: Adenovirus pneumonia is prone to severe clinical and imaging manifestations in children. Bronchoscopic alveolar lavage (BAL) is an important adjunctive therapy for patients with severe imaging findings. The study aimed to evaluate the effect of the timing on the efficacy of bronchoalveolar lavage in children with adenovirus pneumonia., Methods: This study included 134 patients with adenovirus pneumonia treated with BAL at Guangzhou Women and Children's Medical Center from January 2019 to January 2020.They were classified into the severe and mild groups. Based on the timing of BAL, each group was divided into the early BAL layer (received BAL within 1-9 days of the illness course) and the late BAL layer (received BAL within 10-14 days of the illness course). The clinical data of patients with different BAL timings were analyzed in two groups., Results: Among the 134 patients, 70 were categorized into the mild group and 64 were categorized into the severe group. Of the 134 patients, 42 patients received BAL early (mild group: n = 21 and severe group: n = 21) and 92 patients received BAL later (mild group: n = 49 and severe group: n = 43). In the mild group, the fever and hospital duration were shorter in patients who received BAL early than in those who received BAL later (p < 0.05). However, in the severe group, there were no statistically significant differences in the fever and hospital duration between patients who received BAL early and those who received BAL later. However, the need for mechanical ventilation and the incidence of BAL complications, such as new need for oxygen, were higher in patients who received BAL early than in those who received BAL later in the severe group (p < 0.05)., Conclusion: For mild adenovirus pneumonia, early BAL may shorten the fever and hospital duration. However, early BAL in severe cases might not shorten the course of the disease or improve prognosis and may even increase the risks of mechanical ventilation and BAL complications., (© 2021. The Author(s).)

Savin juniper is an excellent species for desertification control in arid and semi-arid areas, where it typically establishes under the protection of nurse plants. Ultimately, established plants emerge into full light as they grow, and this transition is accompanied by an increase in the preponderance of scale-like versus needle-like leaf forms. To test how age and variable light environments affect shade tolerance in savin juniper, we established a pot study under field conditions, with two age cohorts (1- and 4-year-old rooted scions) and three light regimes (10%, 50% and 100% light transmittance). We measured growth, leaf parameters, photosynthesis, chlorophyll fluorescence and foliar pigments on a monthly basis (seven growing months per year, from 2015 to 2017). Overall, there was little interaction among all variables, and both cohort and light regime had significant effects. Leaf form and spacing varied continuously, tending towards shorter, more closely spaced and more appressed scale leaves with higher dry leaf mass per area in older plants or under higher light. There were no clear age-related patterns in carotenoids but both cohort and light had significant effects on gas exchange and chlorophyll fluorescence variables. We conclude that savin juniper shows an intermediate tolerance to shade that changes with growth in that younger plants were less tolerant of full sun than older plants, consistent with its reliance on nurse plants for ultimate establishment in the open., (© 2021 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

The foetus can be regarded as a half-allograft implanted into the maternal body. In a successful pregnancy, the mother does not reject the foetus because of the immune tolerance mechanism at the maternal-foetal interface. The innate immune cells are a large part of the decidual leukocytes contributing significantly to a successful pregnancy. Although the contributions have been recognized, their role in human pregnancy has not been completely elucidated. Additionally, the accumulated evidence demonstrates that the immune checkpoint molecules expressed on the immune cells are co-inhibitory receptors regulating their activation and biological function. Therefore, it is critical to understand the immune microenvironment and explore the function of the innate immune cells during pregnancy. This review summarizes the classic immune checkpoints such as PD-1, CTLA-4 and some novel molecules recently identified, including TIM-3, CD200, TIGIT and the Siglecs family on the decidual and peripheral innate immune cells during pregnancy. Furthermore, it emphasizes the role of the immune checkpoint molecules in pregnancy-associated complications and reproductive immunotherapy., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Introduction: Prevalence of sarcopenia has increased in patients with type 2 diabetes. The influence of glucose-lowering drugs on muscles in these patients remains unclear. We aimed to investigate the association between muscle mass/function and glucose-lowering drugs., Methods: Data of 1042 hospitalized patients with type 2 diabetes were included in this retrospective, cross-sectional study. All the patients had stable hypoglycemic therapy in the last 3 months, and performed bioelectrical impedance analysis, grip strength, and gait speed tests on admission., Results: Skeletal muscle index [6.81 (95% CI 6.67, 6.94) vs. 7.17 (7.09, 7.24) kg/m 2 ], handgrip strength [23.41 (22.24, 24.58) vs. 26.93 (26.33, 27.54) kg], and gait speed [1.19 (1.15, 1.22) vs. 1.27 (1.25, 1.28) m/s] decreased in patients using acarbose compared with the others (all p < 0.001). Gait speed and skeletal muscle index remained lower in patients using acarbose compared to their matched patients in propensity score matching (p = 0.036 and 0.010, respectively). Among drug-naïve patients and patients using insulin, metformin, sulfonylureas, or acarbose monotherapy, the acarbose group had lowest skeletal muscle index and handgrip strength [6.81 (6.52, 7.11) kg/m 2 and 22.54 (19.28, 25.79) kg, p = 0.028 and 0.001, respectively]., Conclusion: Acarbose treatment was associated with decreased muscle mass and strength. Assessment and exercise of muscles in patients with long-term acarbose treatment should be considered., (© 2021. The Author(s).)

Background: China has introduced a series of stricter policies to criminalize drunk driving and increase penalties since May 2011. However, there is no previous study examining the time-varying impacts of drunk driving regulations on road traffic fatalities based on daily data., Methods: We collected 6536 individual data of road traffic deaths (RTDs) in Guangzhou from 2008 to 2018. The quasi-Poisson regression models with an inclusion of the intervention variable and the interaction of intervention variable and a function of time were used to quantify the time-varying effects of these regulations., Results: During the 11-year study period, the number of population and motor vehicles showed a steady upward trend. However, the population- and motor vehicles- standardized RTDs rose steadily before May 2011, the criminalizing drunk driving intervention was implemented and gradually declined after that. The new drunk driving intervention were associated with an average risk reduction of RTDs (ER = -9.01, 95% eCI: - 10.05% to - 7.62%) during the 7.7 years after May 2011. On average, 75.82 (95% eCI, 54.06 to 92.04) RTDs per 1 million population annually were prevented due to the drunk driving intervention., Conclusion: These findings would provide important implications for the development of integrated intervention measures in China and other countries attempting to reduce traffic fatalities by stricter regulations on drunk driving., (© 2021. The Author(s).)

Drinking behavior in rodents is characterized by stereotyped, rhythmic licking movement, which is regulated by the basal ganglia. It is unclear how direct and indirect pathways control the lick bout and individual spout contact. We find that inactivating D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the ventrolateral striatum (VLS) oppositely alters the number of licks in a bout. D1- and D2-MSNs exhibit different patterns of lick-sequence-related activity and different phases of oscillation time-locked to the lick cycle. On the timescale of a lick cycle, transient inactivation of D1-MSNs during tongue protrusion reduces spout contact probability, whereas transiently inactivating D2-MSNs has no effect. On the timescale of a lick bout, inactivation of D1-MSNs (D2-MSNs) causes rate increase (decrease) in a subset of basal ganglia output neurons that decrease firing during licking. Our results reveal the distinct roles of D1- and D2-MSNs in regulating licking at both coarse and fine timescales., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into functional neural cells has been widely investigated for treating neural diseases. However, the limited neural differentiation of BMSCs remains a big challenge to overcome. Herein, for the first time, ginseng-derived exosomes (G-Exos) were demonstrated to have excellent efficiency in stimulating the neural differentiation of BMSCs by transferring the incorporated miRNAs to BMSCs efficiently. In vivo, a photo-cross-linkable hydrogel with chemokine and G-Exos loaded shows strong efficacy in recruiting and directing the neural differentiation of BMSCs in the program. G-Exos were demonstrated to be promising nanoplatforms in transferring plant-derived miRNAs to mammalian stem cells for neural differentiation both in vitro and in vivo, possessing great potential in neural regenerative medicine.

The heptafluoroisopropyl group (CF(CF 3 ) 2 ) is prevalent in pharmaceuticals and agrichemicals. However, heptafluoroisopropoxylated (OCF(CF 3 ) 2 ) compounds remain largely underexplored, presumably due to the lack of efficient access to these compounds. Herein, we disclose the practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox-active N-OCF(CF 3 ) 2 reagents. These reagents were readily prepared from the oxidative heptafluoroisopropylation of hydroxylamines with AgCF(CF 3 ) 2 . The substitutions on the nitrogen atom significantly affected the properties and reactivities of N-OCF(CF 3 ) 2 reagents. Accordingly, two types of N-OCF(CF 3 ) 2 reagents including N-OCF(CF 3 ) 2 phthalimide A and N-OCF(CF 3 ) 2 benzotriazolium salt O' were used as OCF(CF 3 ) 2 anion and radical precursors, respectively. This protocol enables the direct heptafluoroisopropoxylation of a range of substrates, delivering the corresponding products in moderate to excellent yields., (© 2021 Wiley-VCH GmbH.)

The V protein of Newcastle disease virus (NDV) has been shown to inhibit the secretion of interferon (IFN) during infection, which is responsible for the promotion of NDV pathogenicity. However, the ability of the V protein to suppress host innate immunity is not well understood. In this study, we explored the function of V protein and its relationship with virulence by generating V protein-inserted recombinant (r) NDVs. Using rNDVs as a model, we examined the efficiency of infection, IFN responses, and apoptosis of host cells during infection. We found that viral propagation occurred smoothly when V protein from lentogenic NDV is inserted instead of the V protein from the velogenic strain. The infection of lentogenic V protein-inserted rNDV induced less expression of IFNs and downstream antiviral proteins via efficient degradation of p-STAT1 and MDA5. Moreover, velogenic V protein triggered a higher apoptosis rate during infection thereby restricting the replication of NDV. Conversely, lentogenic V protein inhibits IFN responses efficiently and induces less apoptosis compared to the velogenic strain. Our findings provide a novel understanding of the role of V protein in NDV pathogenicity., (Copyright © 2021. Published by Elsevier B.V.)

Background: Previous studies have indicated a negative correlation between GRK2 expression and pain development and transmission. Here, we investigated whether G-protein-coupled receptor kinase 2 (GRK2) was involved in regulating diabetic mechanical hyperalgesia (DMH)., Methods: The adeno-associated viral vectors containing the GRK2 gene (AAV-GRK2) were used to up-regulate GRK2 protein expression. The expression of GRK2 and exchange protein directly activated by cyclic adenosine monophosphate 1 (Epac1) in the dorsal root ganglion (DRG) of lumbar 4-6 was detected via immunoblotting and immunohistochemistry, and the transfection of the GRK2 gene was detected by immunofluorescence., Results: Low levels of GRK2 were able to sustain STZ-induced pain in DMH rats. Intrathecal injection of AAV-GRK2 vector up-regulated GRK2 expression, providing pain rain to rats with DMH. With an increase in DMH duration, there was a decrease in paw withdrawal threshold (PWT) value, aggravating the pain, resulting in a decreasing pattern in GRK2 protein expression over time, whereas Epac1 protein expression showed an opposite trend., Conclusion: GRK2 expression regulated DMH progression and is expected to play a role in the development of targeted therapy for DMH. GRK2 and Epac1 expressions play a vital role in maintaining pain in DMH rats., (© 2021 European Pain Federation - EFIC®.)

Purpose: The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients., Methods: The occurrence of postoperative pneumonia was assessed in 4-6 months (PPFS), 7-12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis., Results: During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1-3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST., Conclusion: PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes., Competing Interests: The authors report no conflicts of interest in this study., (© 2021 Lin et al.)

Precise synthesis and efficient self-assembly of semiconducting polymers are of great interest. Herein, we report the controlled synthesis of π-conjugated poly(phenyl isocyanide)- b -poly(phenyleneethylene) (PPI- b -PPE) copolymers via chain extension of ethynyl 4-iodobenzene initiated by Pd(II)-terminated helical poly(phenyl isocyanide) (PPI). The in-situ-generated block copolymers self-assembled into various supramolecular architectures depending on the PPE length. The helical PPI segment induced the block copolymers with an appropriate PPE length self-assemble into helical nanofibers with a controlled size and defined helicity. Interestingly, the chiral assemblies of the block copolymers exhibit intense optical activity and emit clear circularly polarized luminescence.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422 TN -GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 10 3 -5 × 10 4 of G422 TN -GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5-9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Anti-tumour necrosis factor (TNF)-α drugs are used by increasing numbers of reproductive-age women. Although the neonatal outcomes have been described, there are concerns regarding the risk of infection in offspring following exposure to anti-TNF-α., Methods: A literature search was conducted using Pubmed, EMBASE, and the Cochrane Database, from inception through August 2020. We evaluated the risk of infection in autoimmune disease (AID) offspring unexposed to anti-TNF-α compared to AID offspring exposed to anti-TNF-α, as well as to unexposed non-AID offspring., Results: Our primary analysis showed that both AID offspring unexposed to anti-TNF-α [risk ratio (RR) 1.09; 95% confidence interval (CI), 1.03-1.16; I 2 =0%] and AID offspring exposed to anti-TNF-α (RR 1.39; 95% CI, 1.2-1.61; I 2 =0%] was associated with an increased risk of infection during the first year of life compared with the unexposed non-AID offspring. However, our secondary analysis demonstrated that AID offspring exposed to anti-TNF-α was not associated with an increased risk of infection when compared with AID offspring unexposed to anti-TNF-α (RR=1.1; 95% CI, 0.86-1.4)., Conclusion: Our results suggest that in utero exposure to anti-TNF-α does not appear to increase the risk of infection during the first year of life in the offspring; however, AID itself was associated with a marked excess risk of infection in the children., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

This work describes a base-mediated borylsilylation of benzylic ammonium salts to synthesize geminal silylboronates bearing benzylic proton under mild reaction conditions. Deaminative silylation of aryl ammonium salts was also achieved in the presence of LiO t Bu. This strategy which is featured with high efficiency, mild reaction conditions, and good functional group tolerance provides efficient routes for late-stage functionalization of amines.

Objective: Preeclampsia is a pregnancy-specific disorder that is a major cause of maternal and foetal morbidity and mortality, with a prevalence of 6-8% of pregnancies. Although the downregulation of lysyl oxidase (LOX) and LOX-like protein 2 (LOXL2), which leads to reduced trophoblast cell migration and invasion through activation of the TGF-β1/Smad3/collagen pathway, is relevant to preeclampsia, the mechanisms regulating differences in the gene expression of LOX and LOXL2 in placentas are not yet understood. This study aimed to investigate the mechanisms regulating differences in the gene expression of LOX and LOXL2 in placentas., Methods: The expression of miRNAs, LOX and LOXL2 in preeclamptic placentas and control placentas was analysed by qPCR. Localisation of miR29a and LOXL2 in preeclamptic placentas was performed by RNA-Fluorescence in-situ hybridization assay. The direct regulation of LOXL2 by miR-29a was assessed by dual-luciferase reporter assays in human extravillous trophoblast cells (HTR8/SVneo). Cell migration and invasion were evaluated by Transwell assays in HTR8/SVneo cells., Results: miR-29a expression was upregulated in preeclamptic placentas and negatively correlated with LOXL2 mRNA expression levels. RNA-Fluorescence in-situ hybridization assay revealed a clear overlap between miR-29a and LOXL2 in the placentas of preeclampic women. LOXL2 was a direct target gene of miR-29a, as confirmed by a dual-luciferase reporter assay in HTR8/SVneo trophoblast cells. miR-29a suppressed HTR8/SVneo trophoblast cell migration and invasion. LOXL2 overexpression reversed the inhibitory effects of miR-29a on HTR8/SVneo trophoblast cell migration and invasion., Conclusion: Our results suggest that the upregulation of miR-29a suppresses the migration and invasion of HTR8/SVneo trophoblast cells by directly targeting LOXL2 in preeclampsia., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The family Flavobacteriaceae forms a major branch within the phylum Bacteroidetes. Whole-genome sequence-based analysis could significantly improve the accuracy of taxonomic assignments. In this study, phylogenomic analyses were carried out to revisit the taxonomic status of a clade of the family Flavobacteriaceae. Taking genome-based phylogeny as the primary guideline and average amino acid identity and phenotypic information as supplements, the following taxonomic proposals were put forward: Arenitalea lutea should be reclassified into the genus Algibacter; Algibacter aquaticus should be reclassified into the genus Flavivirga; Jejuia pallidilutea and Algibacter aestuarii should be reclassified into the genus Hyunsoonleella; Algibacter alginicilyticus should be reclassified into the novel genus Pseudalgibacter gen. nov. This study builds up a solid framework for taxonomic decisions of a clade of the family Flavobacteriaceae and will contribute to further insights into the evolution of this family., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The prostate transmembrane protein, androgen induced 1 (PMEPA1) is differentially expressed in pan-cancer. However, PMEPA1 specific role in cancers has not been fully clarified. This study aims to explore the potential role of Pmepa1 in pan-cancer and specific cancer, with a view to deepening the research on the pathological mechanism of cancer., Main Methods: The Perl language and R language were used to identify the correlation between PMEPA1 expression level and clinical indicators, prognosis values, tumor microenvironment, immune cells' infiltration, immune checkpoint genes, TMB and MSI. The Therapeutic Target Database was used for identifying potential therapeutic drugs that target the pathways that are significantly affected by PMEPA1 expression., Key Findings: PMEPA1 differential expression significantly correlated with patients' age, race, tumors' stage and status. PMEPA1 high expression was closely correlated with poor prognosis in many cancer types, excluding prostate adenocarcinoma. PMEPA1 expression was closely related to tumor cells and the immune microenvironment in stromal and immune cells' level, immune cells' infiltration, immune checkpoint genes, tumor mutational burden and microsatellite instability. We also found that the activity of the olfactory transduction pathway was closely related to PMEPA1 expression. In pan-cancer, Trifluoperazine and Halofantrine have the potential to reduce PMEPA1 expression., Significance: This study integrated existing data to explore PMEPA1 potential function in cancers, provided insights for the future cancer-related studies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pentafluorosulfanyl chloride (SF 5 Cl) is the most prevalent reagent for the incorporation of SF 5 group into organic compounds. However, the preparation of SF 5 Cl often relies on hazardous reagents and specialized apparatus. Herein, we described a safe and practical synthesis of a bench-stable and easy-to-handle solution of SF 5 Cl in n-hexane under gas-reagent-free conditions. The synthetic application of SF 5 Cl was demonstrated through the unprecedented reaction with diazo compounds. The chemoselective hydro- and chloropentafluorosulfanylations of α-diazo carbonyl compounds were developed in the presence of K 3 PO 4 or copper catalyst, respectively. These reactions provide a direct and efficient access to various α-pentafluorosulfanyl carbonyl compounds of high value for potential applications., (© 2021 Wiley-VCH GmbH.)

This article examines the relationship of effort-reward imbalance (ERI) on employee stress by considering job burnout (BO), organizational (in)justice (OJ), and sensitivity to terrorism (STT). This study uses the effort-reward imbalance (ERI) framework as a job stress model. After describing terrorism and a brief discussion on organizational justice and some of its challenges, we introduced "sensitivity to terrorism" as a moderator in the ERI framework. Using a 432 sample size of questionnaire data collected from two big cities where terrorist attacks are rampant and received during a period when terrorist attacks were at a peak. After analyzing data in EFA, results from the hierarchical regression analysis provided support for our developed model. Overall, the statistical model is significant ( p < 0.05). We found significant relationships between ERI and facets of BO. Organizational (in)justice mediated the influence of ERI on facets of BO. We also found that STT significantly moderated ERI and facets of burnout. The article concludes with some implications and guidelines for future research., 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 Soomro, Gadehi, Xu and Shaikh.)

A novel arylation of sulfonamides with boronic acids to afford numerous diaryl sulfones via a visible light-mediated N-S bond cleavage other than the typical transition-metal-catalyzed C(O)-N bond activation is described. This methodology, which represents the first catalyst-free protocol for the sulfonylation of boronic acids, is characterized by its simple reaction conditions, good functional group tolerance and high efficiency. Several successful examples for the late-stage functionalization of diverse sulfonamides indicate the high potential utility of this method in pharmaceutical science and organic synthesis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: This study was performed to evaluate the function and satisfaction outcome of patients with rheumatoid arthritis (RA) who underwent total knee arthroplasty (TKA) with high-flexion prostheses., Materials and Methods: Twenty-two patients (35 knees) using high-flexion prostheses (Zimmer, Warsaw, IN) were followed up for a period of 7-11 years from February 2007 to December 2009. Clinical and radiographic follow-up was performed using Hospital for Special Surgery (HSS), Short-Form 36 scores (SF-36), American Knee Society score (KSS), and Knee Society Total Knee Arthroplasty Roentgenographic Evaluation and Scoring System. Patient satisfaction assessments took place at the final follow-up sessions using the Marsh Satisfaction Questionnaire., Results: The average ROM improved from preoperative 68.43° ± 33.78° to 95.54° ± 7.03° at the final follow-up. The HSS score and KSS score for pain improved from (46.49 ± 12.73) points to (85.46 ± 3.90) points and from 20.57 ± 5.91 points to 47.43 ± 3.51 points at the follow-up evaluation, respectively. Physical Component Summary(PCS) and Physical Component Summary (MCS) scores were 45.38 and 52.56, respectively by the end of follow-up. Deep venous thrombosis developed in one patient and one patient required surgical revision due to infection. There were no instances of prosthetic loosening. The satisfaction rate of patients was 95.5%., Conclusion: Although this particular model of TKA did not yield high-flexion angles (ie, 140°) required for kneeling, squatting, or rising from the floor, significant clinical and radiographic gains were evident in these patients with RA., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Growing studies have demonstrated that long non-coding RNA (lncRNA) can act as crucial roles during the progression of various tumors, including colorectal carcinoma (CRC). We aimed to determine lncRNA endogenous bornavirus-like nucleoprotein (EBLN3P) expression in CRC and examine its influence on tumor behaviors of CRC cells. Materials and Methods: Quantitative real-time polymerase chain reaction was used to determine the expression levels of EBLN3P and miR-323a-3p in CRC tissues and cell lines. Cell viability, migration, invasion, and apoptosis were assessed by Cell Counting Kit 8, colony formation, Transwell assay, wound healing assays, and flow cytometry. Bioinformatics and dual-luciferase assays were used to investigate the interaction between EBLN3P and miR-323a-3p, as well as between miR-323a-3p and U2AF homology motif kinase 1 (UHMK1). Western blot was applied for detecting the expressions of the related proteins. Results: EBLN3P was highly expressed in CRC, and its high expression was distinctly associated with increased tumor size, histology/differentiation and advanced TNM stage, and poor clinical outcome of CRC patients. EBLN3P silencing significantly inhibited the proliferation and metastasis and induced the apoptosis of CRC cells. Mechanistically, overexpression of EBLN3P exhibited tumorigenic effects through downregulating the inhibitory effects of miR-323a-3p on UHMK1 expression. The correlation analysis confirmed the positive or negative association among EBLN3P, miR-323a-3p, and UHMK1. Conclusion: EBLN3P promoted the development of CRC via targeting miR-323a-3p/UHMK1, which provided a new idea for treating CRC., 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 Xu, Song, Li, Huang, Liu, Bao and Shen.)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. Nitrated α-synuclein (α-syn) in the blood is a potentially efficient biomarker for PD in its early stages. In this work, an ultrasensitive electrochemical immunosensor was developed for the specific detection of nitrated α-syn. Supramolecule-mediated AuNP composites (GNCs) were modified on the gold electrode as a sensing film to capture anti-nitrated α-syn. Basic characterization studies revealed that GNCs were composed of abundant binding sites and had high conductivity with a large surface area, biocompatibility, and remarkable electrochemical activity. Anti-α-syn-modified magnetic nanoparticles (MNPs) were used as signal amplification tags to construct a sensitive sandwich assay. With a high specific surface area, strong conductivity, and abundant active sites, GNCs as an amplifying matrix can enhance the performance of the immunoassay and obtain preliminary signal amplification. MNPs showed excellent stability and led to a net decrease in the charge-transfer resistance due to their unique spherical structure and high conductivity, resulting in a sensitive electrochemical signal change according to the nitrated α-syn concentration in the sample. Therefore, this simple nitrated α-syn immunoassay with sensitivity and selectivity has potential for practical clinical applications.

In this issue of Neuron, Zhu et al. (2021) reveal that activities in posterior substantia innominate (pSI) neurons that project to the periaqueductal gray (PAG) are both necessary and sufficient to drive aggressive attacks in mice under various conditions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cardiovascular diseases are the leading cause of death in the world due to the high incidence of the diseases coupled with the limited therapeutic options. In recent years, advances in regenerative medicine have emerged as a promising treatment. Differentiation of induced pluripotent stem cells (iPSCs) into cardiac cells and emerging technologies allowing arrangement of cells into complex 3D tissue-like structures open new frontiers for transplantation and engraftment of these tissue patches onto the damaged heart. Despite the cells integrating and presenting initial neovascularization, the functional and electric properties of these patches are still not comparable with those of the host cardiac tissue. Future research optimizing maturation and integration of the iPSC-derived cardiomyocytes is paramount for cardiac cell therapy to attain clinical use. Herein, we will review the state of the art and the different approaches to constructing these 3D transplantable structures.

Background: Cancer-related chronic pain is reported by many patients during treatment. There are very few Chinese tools for measuring psychological inflexibility caused by cancer pain, particularly with regard to psychological processes that might influence pain severity and function disorder during cancer treatment., Objective: To culturally adapt the Psychological Inflexibility in Pain Scale (PIPS) to Chinese cancer patients experiencing chronic pain, including the determination of psychometric properties of the translated PIPS., Methods: This cross-sectional study included 2 phases: (1) translation and cultural adaptation and (2) determination of psychometric properties of the translated PIPS. In total, 389 cancer patients with several types of cancer experiencing chronic pain enrolled from May to September 2018 at a tertiary cancer hospital in Yuelu District of Hunan Province, China., Results: The Chinese PIPS version was semantically equivalent to the original. It had a 2-factor structure with satisfactory content validity (content validity index = 0.78-1.00), convergent and discriminant validity (composite reliability and average variance extracted at 0.41-0.89, P < .001), criterion-related validity (r = 0.54 and 0.41, P < .001), Cronbach's α coefficients (α = .87), and test-retest reliability (0.9 ≤ r ≤ 0.98)., Conclusions: The Chinese PIPS version has been culturally adapted and has strong psychometric properties. The scale is a psychometrically sound assessment of psychological inflexibility that can be used for future studies of pain and pain management for cancer patients., Implications for Practice: The study provides a vital tool for the psychological management of cancer patients with chronic pain., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc.)

Oral lichen planus (OLP), defined as a potential for malignant transformation, is a chronic inflammatory disease in which abnormal angiogenesis serves a role in the malignant changes of the disease. OLP-associated fibroblasts (OLP-MFs), derived from the stroma of OLP tissues, are characterized by the presence of myofibroblasts and contribute to the secretion of pro-inflammatory cytokines, which may be involved in the molecular pathogenesis of OLP. However, the associated mechanisms of angiogenesis in OLP remain unknown. The present study aimed to verify the expression of intercellular adhesion molecular 1, vascular cell adhesion molecule 1, VEGF and CD34 in OLP, and to investigate whether IL-6 secreted by OLP-MFs promoted OLP angiogenesis and the effect of its corresponding antibody inhibition. The results of the experiments demonstrated that inflammation was present and OLP upregulated the secretion of IL-6 by OLP stromal fibroblasts, thereby enhancing OLP angiogenesis. Anti-IL-6 receptor antibody inhibited OLP-stroma IL-6 signaling and suppressed OLP angiogenesis. The antibody inhibited the inflammatory response by inhibiting the secretion of inflammatory factors, including IL-6, to suppress angiogenesis and reduce disease progression, thus indicating that this could be a potential target to develop a treatment for OLP., (Copyright: © Xu et al.)

Strategies to direct the differentiation of endogenous bone marrow derived mesenchymal stem cells (BMSCs) in vivo following recruitment to the injured site are critical to realizing the potential of stem cell-based therapies. But the differentiation efficiency of BMSCs remains limited without direction. Here we demonstrated a novel strategy to promote neuronal differentiation of BMSCs using cross-linked polyethylenimine (PEI) grafted graphene oxide (GO) as the enzyme responsive vector for delivering active genes to BMSCs. In vivo, a core-shell microfiber arrayed hydrogel with a chemokine (SDF-1α) and the cross-linked GO-PEI/pDNAs-bFGF microparticles incorporated into the shell and core, respectively, were constructed. The arrayed hydrogel was shown to recruit and stimulate the neural-like differentiation of BMSCs effectively by delivering the CXCL12 and GO-PEI/pDNAs-bFGF in a self-controlled manner. With this strategy, both in vitro and in vivo neuronal differentiation of BMSCs with function were accelerated significantly. The cross-linked GO-PEI mediated gene transfection together with a multi-functional microfiber arrayed hydrogel provide a translatable approach for endogenous stem cell-based regenerative therapy.

Reported herein is a direct and efficient route to 1-bromo-1-fluoroalkanes through the reaction of unactivated alkenes with dibromofluoromethane under photoredox catalysis. The key to the success of these addition reactions is the employment of a suitable photoredox catalyst. In particular, hydro- and bromo-bromofluoromethylated products were chemoselectively formed using THF and DMF/H 2 O as solvents, respectively. Furthermore, the synthetic application of the prepared 1-bromo-1-fluoroalkanes has been demonstrated by their transformation into a variety of fluorine-containing compounds.

Non-viral platforms can be applied rapidly and cost-effectively for chimeric antigen receptor (CAR)-T cell manufacturing. In the present paper, we describe in detail a clinically relevant manufacturing process for NKG2D CAR-T cells through electroporation of CAR-encoding piggyBac transposon plasmids and in vitro expansion with K562 artificial antigen-presenting cells. With an optimized protocol, we generated the final cell therapy products with 89.2% ± 10.2% NKG2D CAR-positive cells and achieved the corresponding antigen-dependent expansion between 50,000 and 60,000 folds within 4 weeks. To facilitate repeated CAR-T cell infusions, we evaluated the practicality of cryopreservation followed by post-thaw expansion and an extended manufacturing process for up to 9 rounds of weekly K562 cell stimulation. We found that neither compromised the in vitro anti-tumor activity of NKG2D CAR-T cells. Interestingly, the expression of T cell exhaustion markers TIGIT, TIM3, and LAG3 was reduced with extended manufacturing. To enhance the safety profile of the NKG2D CAR-T cells, we incorporated a full-length CD20 transgene in tandem with the CAR construct and demonstrated that autologous NK cells could mediate efficient antibody-dependent cell-mediated cytotoxicity to remove these CAR-T cells. Collectively, our study illustrates a protocol that generates large numbers of efficacious NKG2D CAR-T cells suitable for multiple rounds of infusions., Competing Interests: S.W., J.C.K.T., Y.Y.N., and Z.L. have filed patent applications related to CAR technology and could potentially receive licensing royalties in future., (© 2021 The Author(s).)

Previous studies have suggested that there is a positive correlation between prostate-specific antigen (PSA) levels and prostate volume (PV). A better understanding of the possible influence of PV on a ratio of free to total PSA (f/tPSA) may improve the diagnostic value of the prostate disease. The study group consisted of 342 men with lower urinary tract symptoms (LUTS). All patients underwent urinary tract ultrasonography and had tests carried out on PSA, serum glucose, total cholesterol, triglyceride, HDL, LDL and blood pressure. Univariate and multivariate analyses were used to assess the associations between prostate volume and f/tPSA value. We found no obvious relationship between prostate volume and f/tPSA value when PSA >10 ng/ml but did observe a positive correlation when 4 ng/ml < PSA ＜ 10 ng/ml (hazard ratio [HR]: 0.0012; 95% confidence interval [CI]: 0.0009-0.0248). With increasing prostate volume, multivariate analysis showed an obvious increase in f/tPSA value (HR: 0.0011; 95% CI: 0.0007-0.0015) (p ≤ .0001). We confirmed that prostate volume could affect the f/tPSA levels in serum. There was an obvious positive correlation between prostate volume and f/tPSA level when PSA levels were between 4 and 10ng/dl. There was no significant correlation between prostate volume and f/tPSA value when PSA >10 ng/ml., (© 2020 Wiley-VCH GmbH.)

Rationale: Dihydroresveratrol has been demonstrated to possess a wide spectrum of bioactivities, such as anti-oxidant and anti-inflammatory effects. The aim of the present study was to investigate the metabolic profiles of dihydroresveratrol in rats., Methods: The in vitro metabolism was elucidated by incubating dihydroresveratrol with rat hepatocytes for 2 h at 37°C. For in vivo metabolism, dihydroresveratrol was orally administered to rats at a single dose of 50 mg/kg and the resulting biliary and urinary samples were collected. All the samples were analyzed by liquid chromatography combined with electrospray ionization high-resolution mass spectrometry. The structures of the metabolites were proposed based on their accurate masses and their MS/MS product ions., Results: A total of 16 metabolites including three phase I metabolites and 13 phase II metabolites were detected and structurally proposed. Among these metabolites, M6 and M14 were unambiguously identified as 3'-hydroxylresveratrol and resveratrol, respectively, using reference standards. Dihydroresveratrol was mainly metabolized into resveratrol (M14) and a glucuronide conjugate (M12), which were excreted into urine and bile as the major metabolites., Conclusions: The metabolic pathways of dihydroresveratrol involved hydroxylation, dehydrogenation, glucuronidation, glutathione (GSH) conjugation and methylation. The present study provided useful information with regard to the metabolic profiles of dihydroresveratrol in rats., (© 2020 John Wiley & Sons Ltd.)

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14 C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14 C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka., Competing Interests: The authors declare no competing interest.