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Abstract The exploration of chemical space holds promise for developing influential chemical entities. Molecular representations, which reflect features of molecular structure in silico, assist in navigating chemical space appropriately. Unlike atom-level molecular representations, such as SMILES and atom graph, which can sometimes lead to confusing interpretations about chemical substructures, substructure-level molecular representations encode important substructures into molecular features; they not only provide more information for predicting molecular properties and drug‒drug interactions but also help to interpret the correlations between molecular properties and substructures. However, it remains challenging to represent the entire molecular structure both intactly and simply with substructure-level molecular representations. In this study, we developed a novel substructure-level molecular representation and named it a group graph. The group graph offers three advantages: (a) the substructure of the group graph reflects the diversity and consistency of different molecular datasets; (b) the group graph retains molecular structural features with minimal information loss because the graph isomorphism network (GIN) of the group graph performs well in molecular properties and drug‒drug interactions prediction, showing higher accuracy and efficiency than the model of other molecular graphs, even without any pretraining; and (c) the molecular property may change when the substructure is substituted with another of differing importance in group graph, facilitating the detection of activity cliffs. In addition, we successfully predicted structural modifications to improve blood‒brain barrier permeability (BBBP) via the GIN of group graph. Therefore, the group graph takes advantages for simultaneously representing molecular local characteristics and global features. Scientific contribution The group graph, as a substructure-level molecular representation, has the ability to retain molecular structural features with minimal information loss. As a result, it shows superior performance in predicting molecular properties and drug‒drug interactions with enhanced efficiency and interpretability.

Abstract Background Intravenous fluid administration and prophylactic vasopressor infusion are the primary methods for preventing spinal anesthesia-induced hypotension during cesarean delivery. However, evidence regarding the impact of different volumes of crystalloid solution on the phenylephrine infusion dosage for preventing this hypotension remains inconclusive. This study aimed to determine the effect of two IV fluid infusion rates (10 or 20 mL/kg/h) on phenylephrine requirement for preventing spinal anesthesia-induced hypotension. Methods Eighty healthy parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled. Participants were randomly assigned to receive either 10 mL/kg/h (group 10) or 20 mL/kg/h (group 20) of lactated Ringer’s solution. The first patient in each group received 0.5 µg/kg/min of phenylephrine infusion immediately after intrathecal injection. The phenylephrine dose in subsequent patients was adjusted by increments or decrements of 0.05 µg/kg/min based on the previous patient’s response. The ED50 of phenylephrine infusion for preventing spinal-induced hypotension for cesarean delivery was estimated using a modified up-down sequential analysis, with probit analysis applied as a backup sensitivity analysis. Results The ED50 values for preventing spinal anesthesia-induced hypotension were 0.30 µg/kg/min (95% CI, 0.29–0.32 µg/kg/min) for group 10, and 0.19 µg/kg/min (95% CI, 0.16–0.22 µg/kg/min) for group 20, respectively. The estimated relative potency for phenylephrine in group 10 compared to group 20 was 1.52 (95%CI, 1.24–1.97), showing a significant difference in the ED50 values between the two groups. Conclusion This study found that a higher crystalloid co-loading rate significantly reduces prophylactic phenylephrine requirement for preventing spinal anesthesia induced hypotension. Trials registration https://www.chictr.org.cn/showproj.html?proj=125918 (Trial number: ChiCTR2100048002).

This study explored the protective effect and potential mechanism of carvacrol acetate (CAA) on the oxidation of chlorpyrifos (CPF). A model of oxidative stimulus damage was established in Sprague–Dawley rats by subcutaneous injection of the CPF poison. PC12 cells were used to construct an oxidative injury model using CPF, and the protective effects and mechanism of action of CAA against CPF-induced oxidative damage were explored in vitro. The key role of Nuclear factor erythroid-2-related factor 2 (Nrf2) in alleviating CPF-induced damage via CAA was further confirmed by administering Nrf2 inhibitors to PC12 cells. Administration of CAA significantly enhanced the locomotor ability of the rats, alleviated neuronal pathological alterations, and increased the number of Nissl bodies, while increasing autophagic bodies. In vitro, CAA promoted cell survival and augmented the mitochondrial membrane potential. It decreased both intra- and extracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), while markedly elevating mitochondrial DNA (mtDNA) copy number. Moreover, PC12 cells treated with Nrf2 inhibitors failed to exhibit any improvement in survival rate when treated with CAA after a toxic insult. Furthermore, ROS and MDA levels were not significantly reduced, SOD enzyme activity did not increase, and mitochondrial membrane potential and mtDNA copy number did not improve. Western blot analysis showed that the expression of Tfam, Beclin1, and LC3II/LC3I proteins in the CAA group decreased significantly after Nrf2 inhibition. These findings suggest that CAA modulates mitochondrial function and autophagy by regulating the Nrf2 signalling pathway to mitigate the toxic damage. Finally, the effect of the autophagy inhibitor, 3-MA, on PC12 cells suggests that CAA promotes mitophagy by participating in the Nrf2 pathway, thereby preventing CPF-induced oxidative stress damage.

Aim of the study: To analyze the progress in Mongolian medicine and medicinal materials and to highlight its development process, emerging trends, and hotspots. Materials and methods: Papers on Mongolian medicine and medicinal materials from January 2000 to May 2022 were retrieved from the China National Knowledge Infrastructure (CNKI) database. Using the collaboration network analysis of CiteSpace V and VOSviewer software, the cooperation among individuals and institutions in the field of scientific research was analyzed. The functions of frequency analysis, cluster analysis, and burst analysis were employed to conduct bibliometric analysis on research hotspots and trends in the field of Mongolian medicine research. Furthermore, the data visualization function was utilized to clearly display data trends and changes. Results: A total of 8362 papers on Mongolian medicine medicinal materials from CNKI were identified and analyzed.The research on Mongolian medicine has gone through three stages: the initial stage, the exploratory stage, and the developmental stage. The top two institutions in the number of papers are Inner Mongolia Medical University and Inner Mongolia University for Nationalities. Bagenna from Inner Mongolia Medical University is the author with the most papers. “clinical efficacy”, “clinical research”, and “quality standards” were the most frequently used keywords. Research in the field of Mongolian medicine has focused on several diseases, including skeletal system disorders, cardiovascular diseases, and digestive system disorders. Conclusion: Since 2000, there have been growing attention and efforts made in the field of Mongolian medicine and medicinal materials. The research in the field of Mongolian medicine had undergone three stages, namely the initial stage, the exploratory stage, and the developmental stage. The focus shifted from basic research such as the analysis of medicinal ingredients in Mongolian herbs to the application-oriented directions of traditional treatment techniques and advantageous diseases in Mongolian medicine. To make breakthroughs in this field, further research is needed to improve the persuasiveness and authority of Mongolian medicine and medicinal materials in terms of mechanism, standardization, and safety, to promote the development of Mongolian medicine and medicinal materials.

Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro‐ and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.

Background and aims: Defective enzymes, cofactors, or transporters of metabolic pathways cause inherited metabolic disorders (IMDs), a group of genetic disorders. Several IMDs have serious consequences for the affected neonates. Newborn screening for IMDs is conducted by measuring specific metabolites between 3 and 7 days of life. Herein, we analyzed the incidence, spectrum, and genetic characteristics of IMDs in newborns in the Zhuzhou area.Methods: Tandem mass spectrometry was conducted on 90,829 newborns who were admitted to the Women and Children Healthcare Hospital of Zhuzhou and requested for screening for IMDs. These newborns were subsequently subjected to next-generation sequencing and further validated using Sanger sequencing.Results: 30 IMDs cases were found in 90,829 cases of newborns screened for IMDs, and the overall incidence was 1/3,027. The incidence of amino acid, organic acid, fatty acid oxidation and urea cycle disorders were 1/8,257, 1/18,165, 1/7,569, and 1/45,414, respectively. Additionally, 9 cases of maternal IMDs were found in our study, and unreported gene mutations of 3 cases IMDs were identified.Conclusion: Our data indicated that IMDs are never uncommon in zhuzhou, meanwhile, we also found that primary carnitine deficiency was the only disorder of fatty acid oxidation in Zhuzhou, and the incidence (1/7,569) was higher than the national level, organic acid metabolic diseases are mostly inherited. Therefore, our study has clarified the disease spectrum and genetic backgrounds, contributing to the treatment and prenatal genetic counseling of these disorders in this region.

Lifestyle modification is an effective measure for diabetes prevention in people with prediabetes, but its associations with the long-term risks of cardiovascular disease (CVD), cancer, and mortality remain largely uncertain. We aimed to investigate the associations of combined healthy lifestyle factors with these health outcomes among participants with prediabetes. The study included 121 254 people with prediabetes from four prospective cohorts: the Dongfeng-Tongji (DFTJ) cohort and Kailuan study, both from China; the UK Biobank; and the US National Health and Nutrition Examination Survey (NHANES; for mortality analysis only). We documented a total of 18 333 incident diabetes, 10 829 incident CVD, 6926 incident cancer, and 9877 deaths during follow-up. Combined healthy lifestyle scores (scored from 0 to 5) were constructed based on never smoking or quitting smoking for ≥ 10 years, low-to-moderate alcohol drinking, optimal physical activity, healthy diet, and optimal waist circumference. First, Cox proportional-hazards regression models were used to quantify the associations of combined lifestyle score with health outcomes in each cohort; then, multivariable-adjusted hazard ratios (HRs) were pooled via a random-effects model of meta-analysis. Compared with participants with the least healthy lifestyle (a score of 0–1), participants with the healthiest lifestyle (a score of 4–5) had significantly reduced risks of all outcomes. The HRs (95% confidence interval (CI)) were 0.57 (0.48–0.69) for diabetes, 0.67 (0.62–0.73) for CVD, 0.80 (0.73–0.88) for cancer, and 0.54 (0.42–0.70) for mortality. Significant associations were consistently found across subgroups of baseline demographic characteristics and metabolic health status. In conclusion, our pooled analyses of four cohorts from three countries reveal that greater adherence to a healthy lifestyle is associated with considerably lower risks of diabetes and its major complications among adults with prediabetes. These findings provide informative and compelling evidence for establishing clinical guidelines and public health policies.

Abstract Background and objective Patients on parenteral nutrition (PN) are at high risk of both liver and pancreatic injury. More efforts were focused on liver, however, limited data is available to evaluate the effects of PN on pancreas. Thus, we performed a retrospective observational study to evaluate the association between PN and pancreatic injury in Chinese adult patients. Methods Adult patients (18–80 years), who received PN for a week or longer, and with repeated measurements of pancreatic enzymes, were included in the analysis. Pancreatic injury was confirmed by serum level of pancreatic amylase (P-AMYwas 53 U/L or higher) or lipase (LP was 63 U/L or higher), which were evaluated at baseline and following every week during PN duration. Age, sex, body weight, height, diagnosis of diseases, history of diseases, surgery, white blood cell, c-reactive protein, liver and renal function, fasting blood glucose, lipid profile, and daily energy supplied by PN and enteral nutrition were abstracted from medical records. Results A total number of 190 adult patients (125 men, 65 women) were included in the study. The average age and BMI were 61.8 ± 13.0 years and 21.7±3.3 kg/m2, while medium serum level of P-AMY and LP were 29.0 U/L (quartile range: 18.0, 47.0) and 33.0 U/L (quartile range: 19.0, 58.0), respectively at baseline. The median duration of PN was 15 days (quartile range: 11.0, 21.0). The prevalence of pancreatic injury was 42.1% (80/190) while it was 28.4% (54/190), 43.3% (77/178), 47.8% (44/92) after one-, two-, and three-week or longer PN adminstration. The proportion of daily energy supplement by PN (OR = 3.77, 95%CI: 1.87, 7.61) and history of infection were positively (OR = 3.00, 95%CI: 1.23, 7.36), while disease history for diabetes mellitus (OR = 0.38, 95%CI: 0.15, 0.98) and cancer (OR = 0.46, 95%CI: 0.23, 0.95), were negetively associated with pancreatic injury. Total bile acids were associated with the increment of P-AMY (beta = 0.98, 95%CI: 0.39, 1.56) and LP (beta = 2.55, 95%CI: 0.98, 4.12) by multi-variate linear regression. Conclusion PN was associated with pancreatic injury, as demonstrated by the increase of both serum P-AMY and LP.

Abstract Background Studies are trying to add immunotherapy to gemcitabine and cisplatin (GP) induction chemotherapy, the standard therapy, in nasopharyngeal carcinoma (NPC) patients with locoregionally advanced disease. However, how the immune system responds to GP remains unknown. Method We examined the dynamic changes of circulating immune cells and plasma cytokines in NPC patients administered with GP. Result After GP administration, immunosuppressive myeloid cells, including CD11b+CD14+ monocytes, CD33+ myeloid cells, CD33+CD11+ myeloid cells, total MDSCs (CD33+CD11+HLA‐DR−/low), monocytic MDSCs, and granulocytic MDSCs decreased significantly. The regulatory T cells and B cells, two important suppressive lymphocyte subpopulations, also decreased. On the other hand, the levels of CD3+ T cells, total B cells, central memory CD4+ T cells, and pro‐inflammatory cytokines (including Interleukin [IL]‐1β, IL‐6, IL‐2, IL‐5, and IL‐8) increased significantly after GP administration. Besides, GP chemotherapy did not weaken the cytotoxic activity and proliferative capacity of T cells. Conclusion Our results showed the immune modulation effect of GP induction chemotherapy in locoregionally advanced NPC, providing a solid basis for its combination with immunotherapy.

AIM: To evaluate the effect of miRNA-451 on rhesus macaque choroid-retinal endothelial (RF/6A) cell function and proteome profile. METHODS: The RF/6A cells were transfected with miRNA-451 mimic and inhibitor. The role of miRNA-451 on proliferation ability was evaluated by CCK-8 assay. Furthermore, iTRAQ quantitative proteomic analysis was applied to comprehensively illuminate the change of cellular proteins and biological function between different groups. RESULTS: In miRNA-451 overexpression group, cell proliferation of RF/6A decreased both at 24h and 48h; while in miRNA-451 inhibition group, on the contrary, RF/6A cell proliferation was increased at 48h. Based on iTRAQ quantitative proteomic analysis, 23 differentially expressed proteins (DEPs) were detected in the comparison of miRNA-451 mimic and mimic control-transfected RF/6A cells, and 30 DEPs were identified in the comparison of RF/6A cells transfected with miRNA-451 inhibitor and inhibitor control. DEPs such as GORASP2, KRT1, SLC7A2, RIC8A, DDX42, CAP1, PCBP2 might be closely related to the inhibitory effect of miRNA-451 on RF/6A cell proliferation, while PCYT1A, MGAT1, TUBB, MCU, SIL1, BID, MSH6 might account for the positive effect of miRNA-451 inhibitor on RF/6A cell growth. PTPN1, as the only protein exhibiting an opposite trend between miRNA-451 mimic and inhibitor-transfected cells, was most likely accountable for the inhibition of miRNA-451 mimic on RF/6A cell growth, and the promotion of miRNA-451 inhibitor on RF/6A cell proliferation. CONCLUSION: miRNA-451 overexpression can suppress the growth of RF/6A cells while knockdown of miRNA-451 can promote RF/6A cell viability. Among all DEPs, increased PTPN1 is most likely to account for the negative regulation of miRNA-451 on RF/6A proliferation. miRNA-451 can be a protective factor for neovascular disease of fundus via regulating choroid retinal endothelial cell function.

Abstract Background Ring chromosomes can be formed by terminal breaks of two arms of a chromosome and their rejoining, leading to a loss of genetic material. They may also be formed by telomere-telomere fusions with no deletion, resulting in the formation of a complete ring. Mosaic X-ring chromosomes are extremely rare and have highly variable phenotypes. Here, we report a case with a mosaic X-ring chromosome in a patient with Turner syndrome, and we illustrate the unreported complicated mechanism using chromosome analysis and fluorescence in situ hybridization (FISH). Case presentation A 10-year-old girl of short stature presenting Turner syndrome was admitted to our hospital. The patient’s clinical characteristics were subsequently documented. Genetic analysis showed a karyotype of mostly 45,X[140]/46,X,r(X)[60]. The X ring chromosome was cytogenetically characterized as 45,X/46,X,r(X)(p22.32q21.1), with a length of approximately 74 Mb. Conclusions Taken together, we report a rare case with a mosaic X ring chromosome in Turner syndrome and we believe this case expands our collective knowledge of mosaic structural chromosomal disorders and provides new insight into clinical management and genetic counseling for Turner syndrome.

Our previous RNA sequencing study showed that the long non-coding RNA ischemia-related factor Vof-16 (lncRNA Vof-16) was upregulated after spinal cord injury, but its precise role in spinal cord injury remains unclear. Bioinformatics predictions have indicated that lncRNA Vof-16 may participate in the pathophysiological processes of inflammation and apoptosis. PC12 cells were transfected with a pHBLV-U6-MCS-CMV-ZsGreen-PGK-PURO vector to express an lncRNA Vof-16 knockdown lentivirus and a pHLV-CMVIE-ZsGree-Puro vector to express an lncRNA Vof-16 overexpression lentivirus. The overexpression of lncRNA Vof-16 inhibited PC12 cell survival, proliferation, migration, and neurite extension, whereas lncRNA Vof-16 knockdown lentiviral vector resulted in the opposite effects in PC12 cells. Western blot assay results showed that the overexpression of lncRNA Vof-16 increased the protein expression levels of interleukin 6, tumor necrosis factor-α, and Caspase-3 and decreased Bcl-2 expression levels in PC12 cells. Furthermore, we established rat models of spinal cord injury using the complete transection at T10. Spinal cord injury model rats were injected with the lncRNA Vof-16 knockdown or overexpression lentiviral vectors immediately after injury. At 7 days after spinal cord injury, rats treated with lncRNA Vof-16 knockdown displayed increased neuronal survival and enhanced axonal extension. At 8 weeks after spinal cord injury, rats treated with the lncRNA Vof-16 knockdown lentiviral vector displayed improved neurological function in the hind limb. Notably, lncRNA Vof-16 knockdown injection increased Bcl-2 expression and decreased tumor necrosis factor-α and Caspase-3 expression in treated animals. Rats treated with the lncRNA Vof-16 overexpression lentiviral vector displayed opposite trends. These findings suggested that lncRNA Vof-16 is associated with the regulation of inflammation and apoptosis. The inhibition of lncRNA Vof-16 may be useful for promoting nerve regeneration and functional recovery after spinal cord injury. The experiments were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

AIM: To evaluate therapeutic outcomes of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) treatment in patients with refractory uveitis. METHODS: A retrospective and noncomparative review was performed on four patients with refractory uveitis from December 2013 to December 2017. HUC-MSCs were administered intravenously at a dose of 1×106 cells/kg. Clinical response, relapse rate, change of visual acuity, and other metrics were evaluated. RESULTS: All four patients presented with responses to HUC-MSCs treatment, with three males and one female. The numbers of uveitis attacks per year after the HUC-MSCs treatment (0, 2, 0, 0 respectively) all decreased compared with the numbers before the treatment (3, 6, 4, 4 respectively). The oral steroid and immunosuppressive agents were tapered in all patients without recrudescence of ocular inflammation, and three patients discontinued their oral medicine at the last visit. The best corrected visual acuity (BCVA) of 3 patients was improved to varying degrees, and the BCVA of 1 patient remained at 20/20 (Snellen chart) from the first to the last consultation. CONCLUSION: The study provides an effective therapy of HUC-MSCs in maintaining remission in patients affected by uveitis refractory to previous immunosuppressant treatments.

Abstract We study the thermodynamic properties of asymmetric quark matter, large mass quark stars (QSs), and proto-quark stars (PQSs) within the quasiparticle model. Considering the effects of temperature within quasiparticle model can significantly influence the EOS and the entropy of strange quark matter (SQM), quark fractions in SQM, as well as the tidal deformability and the maximum mass of PQSs along the star evolution line. Our results indicate that the recent discovered heavy compact stars PSR J0348+0432, MSR J0740+6620, PSR J2215+5135, and especially the GW190814’s secondary component $$m_2$$ m 2 can be well described as QSs within the quasiparticle model. The tidal deformability for the QSs describing the heavy compact stars is extremely large, which can not well describe GW170817 as QSs, and the effects of the temperature in the heating process along the star evolution will further increase the tidal deformability and the maximum mass of PQSs.

AIM: To assess the correlation between disorganization of the retinal inner layers (DRIL) and best-corrected visual acuity (BCVA) in patients with uveitis and macular edema (UME) who underwent systemic treatment using optical coherence tomography (OCT). METHODS: A retrospective clinical study of 23 patients (30 eyes) with DRIL and 23 patients (31 eyes) without DRIL secondary to UME were included. All patients underwent comprehensive ophthalmic examinations at baseline, 3, 6, and 12mo after local and systemic treatment. The OCT-based parameters included foveal center point thickness (FCPT), mean thickness (MT), and diameters of DRIL in horizontal and vertical directions. BCVA and OCT-based parameters were compared between the two groups. The relationship between each OCT parameter and BCVA was evaluated using linear correlation and regression analysis. RESULTS: At the initial visit, the mean baseline FCPT was 441.03±128.68 μm in the eyes with DRIL and 337.26±99.31 μm in the eyes without DRIL (P=0.001). No significant differences were observed in MT (P=0.357). The mean size of transverse and vertical diameters of DRIL was 684.07±267.51 and 267.07±104.61 μm at baseline, respectively. There was significant improvement in BCVA and OCT-based parameters at 3, 6, and 12mo in all cases (P

AIM: To report the effectiveness of intravitreal implantation of dexamethasone implant (Ozurdex) after phacoemulsification and intraocular lens implantation in refractory uveitis patients. METHODS: This single-center retrospective study conducted for refractory pan-uveitis patients who underwent cataract surgery combined with intravitreal Ozurdex implantation. The main outcome measurements were best-corrected visual acuity (BCVA), central retinal thickness (CRT), grade of anterior chamber cell (AAC), intraocular pressure (IOP), and systemic/ocular adverse events. RESULTS: Ten eyes of 7 patients were included. BCVA showed significant improvement at 1mo (P=0.004), 3mo (P=0.0004), and 6mo (P=0.001) post operation. There were no statistically significant differences in the postoperative CRT among follow-up groups (P>0.05). No significant differences were observed in the baseline IOP when compared to 1, 3, and 6mo (all P>0.05) post operation. One patient developed a transient elevated IOP post injection. Two eyes (20%) developed posterior capsular opacifications and underwent neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy. In six patients (8 eyes, 71.4%), the systemic steroid usage was reduced to below 10 mg/d. The patients experienced a mean of 1.4±0.52 recurrences of inflammation in the 6mo before operation and 0.7±0.48 in the 6mon post operation. The mean recurrence time was 13±0.58wk (range 12-14wk) post operation. In five of seven patients (7 out of 10 eyes), inflammation relapse was developed postoperatively. Only one patient (2 eyes) needed increased amounts of oral corticosteroids. Intraocular inflammation recurrence in the remaining patients was controlled by topical steroids. CONCLUSION: Ozurdex is considered a safe and effective approach to control postoperative inflammation in cataract surgery for patients with refractory uveitis in our study. After the disappearance of Ozurdex's anti-inflammatory effects over time, in most cases the recurrent inflammation can be controlled by topical steroids.

Abstract We study the thermodynamic properties of asymmetric quark matter and large mass quark stars within the confined-isospin-density-dependent-quark-mass model. We find that the quark matter symmetry energy should be very large in order to describe the recent discovered heavy compact stars PSR J0348+0432 ( $$\text {2.01}\pm \text {0.04}M_{\odot }$$ 2.01 ± 0.04 M ⊙ ), MSP J0740+6620 ( $$\text {2.14}\pm ^\text {0.10}_\text {0.09}M_{\odot }$$ 2.14 ± 0.09 0.10 M ⊙ of 68.3 $$\%$$ % credibility interval and $$\text {2.14}\pm ^\text {0.20}_\text {0.18}M_{\odot }$$ 2.14 ± 0.18 0.20 M ⊙ of 95.4 $$\%$$ % credibility interval) and PSR J2215+5135 (2.27 $$\pm ^\text {0.10}_\text {0.09}M_{\odot }$$ ± 0.09 0.10 M ⊙ ) as QSs. The tidal deformability $$\Lambda _{1.4}$$ Λ 1.4 of the QSs is also investigated in this work, and the result indicates that $$\Lambda _{1.4}$$ Λ 1.4 may depend on the isospin effects and the strength / orientation distribution of the magnetic fields inside the quark stars.

Abstract We present an efficient hyperentanglement concentration protocol (hyper-ECP) for two-photon six-qubit systems in nonlocal partially hyperentangled Bell states with unknown parameters. In our scheme, we use two identical partially hyperentangled states which are simultaneously entangled in polarization and two different longitudinal momentum degrees of freedom (DOFs) to distill the maximally hyperentangled Bell state. The quantum nondemolition detectors based on the cross-Kerr nonlinearity are used to realize the parity checks of two-photon systems in three DOFs. The hyper-ECP can extract all the useful entanglement source, and the success probability can reach the theory limit with the help of iteration. All these advantages make our hyper-ECP useful in long-distance quantum communication in the future.

Long non-coding RNAs (lncRNAs) are abundantly expressed in the central nervous system and exert a critical role in gene regulation via multiple biological processes. To uncover the functional significance and molecular mechanisms of lncRNAs in spinal cord injury (SCI), the expression signatures of lncRNAs were profiled using RNA sequencing (RNA-seq) technology in a Sprague-Dawley rat model of the 10th thoracic vertebra complete transection SCI. Results showed that 116 of 14,802 detected lncRNAs were differentially expressed, among which 16—including eight up-regulated (H19, Vof16, Hmox2-ps1, LOC100910973, Ybx1-ps3, Nnat, Gcgr, LOC680254) and eight down-regulated (Rmrp, Terc, Ngrn, Ppp2r2b, Cox6a2, Rpl37a-ps1, LOC360231, Rpph1)—demonstrated fold changes > 2 in response to transection SCI. A subset of these RNA-seq results was validated by quantitative real-time PCR. The levels of 821 mRNAs were also significantly altered post-SCI; 592 mRNAs were up-regulated and 229 mRNAs were down-regulated by more than 2-fold. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that differentially expressed mRNAs were related to GO biological processes and molecular functions such as injury and inflammation response, wound repair, and apoptosis, and were significantly enriched in 15 KEGG pathways, including cell phagocytosis, tumor necrosis factor alpha pathway, and leukocyte migration. Our results reveal the expression profiles of lncRNAs and mRNAs in the rat spinal cord of a complete transection model, and these differentially expressed lncRNAs and mRNAs represent potential novel targets for SCI treatment. We suggest that lncRNAs may play an important role in the early immuno-inflammatory response after spinal cord injury. This study was approved by the Administration Committee of Experimental Animals, Guangdong Province, China.

Genetic diversity plays an essential role in plant breeding and utilization. Pepper is an important vegetable and spice crop worldwide. The genetic diversity of 1 904 accessions of pepper conserved at the National Mid-term Genebank for Vegetables, Beijing, China was analyzed based on 29 simple sequence repeat (SSR) markers, which were evenly distributed over 12 pepper chromosomes. The pepper accessions were divided into two groups in a genetic structure analysis, and the two groups showed obvious differences in fruit type and geographical distribution. We finally selected 248 accessions capturing 75.6% of the SSR alleles as the core collection for further research. Insights into the genetic structure of pepper provide the basis for population-level gene mining and genetic improvement.

AIM: To investigate the pooled prevalence of diabetic retinopathy (DR), proliferative DR (PDR) and nonproliferative DR (NPDR) in Asian type 2 diabetes mellitus (T2DM) patients. METHODS: We performed a systematic search online search using PubMed, EMBASE, Web of Science, the Cochrane Library, and China WeiPu Library to identify eligible studies that reported the prevalence of DR, PDR and NPDR in Asian T2DM patients. Effect size (ES) with 95% confidence interval (CI) was used to evaluate the prevalence of DR, PDR and NPDR in Asian T2DM patients, respectively. RESULTS: There were 41 references and 48 995 T2DM patients involved in this study. The prevalence of DR, PDR, and NPDR was 28%, 6%, and 27% in T2DM patients, respectively; while the prevalence of PDR and NPDR in DR patients was 17% and 83%, respectively. Subgroup analysis showed that prevalence of DR in T2DM patients from Singaporean, Indian, South Korean, Malaysian, Asian, and Chinese was 33%, 42%, 16%, 35%, 21% and 25%, respectively. In T2DM patients with NPDR from Indian, South Korean, Malaysian, Asian, Chinese, higher prevalence was found than that in PDR patients (45% vs 17%, 13% vs 3%, 30% vs 5%, 23% vs 2% and 22% vs 3%), as well as in DR patients (74% vs 26%, 81% vs 19%, 86% vs 14%, 92% vs 8% and 85% vs 15%). The prevalence of PDR in T2DM from India was higher than patients from other locations of Asia, and the same results were also observed in NPDR patients. CONCLUSION: In either T2DM Asian patients or DR patients, NPDR is more common than PDR. Based on our results, we should pay more attention to NPDR screening and management in T2DM patients, and we also recommend suitable interventions to prevent its progression.

Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α (hypoxia-inducible factor 1α overexpression lentivirus), gel (pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α (pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups (in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area (labeled by CD31 around avulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii (identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

Abstract Background Two health concerns primarily related to triatomine bugs are transmission of Trypanosoma cruzi through infective feces, and allergic reactions induced by triatomine bites. In the Southwestern United States, reduviid bugs bites commonly cause insect allergy. In South China, four cases of anaphylactic shock have been reported after this bite exposure. To further classify the species of these bugs and confirm the sensitization of the triatomine saliva, we caught triatomine bugs from the region where the bites occurred and performed phylogenetic and immunohistochemical (IHC) analysis. Methods Triatomine bugs were collected in Donghai Island of Zhanjiang City in South China. The genomic DNA was extracted from three legs of the bugs. The fragments of mitochondrial 16S rRNA, cytochrome c oxidase subunit I (COI) gene and nuclear ribosomal 18S and 28S rRNA genes were obtained by PCR and sequenced. A phylogenetic tree was constructed based on the sequence of 16S rRNA gene using a maximum likelihood method with MEGA 7.0 software. Trypanosomal specific fragments and vertebrate COI genes were amplified from the fecal DNA to detect the infection of trypanosomes and analyze the blood feeding patterns, respectively. Paraffin-embedded sections were then prepared from adult triatomines and sent for IHC staining. Results We collected two adult triatomine bugs in Donghai Island. Morphological and molecular analyses indicated that the triatomines were Triatoma rubrofasciata. No fragments of T. cruzi or other trypanosomes were detected from the fecal DNA. Mitochondrial gene segments of Homo sapiens and Mus musculus were successfully amplified. The allergens which induced specific IgE antibodies in human serum were localized in the triatomine saliva by IHC assay. Conclusions The two triatomine bugs from Donghai Island were T. rubrofasciata. They had bitten humans and mice. Their saliva should contain the allergens related to the allergic symptoms and even anaphylactic shock of exposed residents. Great consideration should be given to this triatomine bugs due to their considerable distribution and potential threat to public health in South China.

Abstract Background The tumor–node–metastasis (TNM) staging system does not perform well for guiding individualized induction or adjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We attempted to externally validate the Pan’s nomogram, developed based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system, for patients with locoregionally advanced disease. In addition, we investigated the reliability of Pan’s nomogram for selection of participants in future clinical trials. Methods This study included 535 patients with locoregionally advanced NPC who were treated between March 2007 and January 2012. The 5-year overall survival (OS) rates were calculated using the Kaplan–Meier method and compared with predicted outcomes. The calibration was tested using calibration plots and the Hosmer–Lemeshow test. Discrimination ability, which was assessed using the concordance index, as compared with other predictors. Results Pan’s nomogram was observed to underestimate the 5-year OS of the entire cohort by 8.65% [95% confidence interval (CI) − 9.70 to − 7.60%, P

AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS: The streptozotocin (STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus (DM) group (saline, 3 μL/eye); RC28-E at low (0.33 μg/μL, 3 μL), medium (1 μg/μL, 3 μL), and high (3 μg/μL, 3 μL) dose groups; vascular endothelial growth factor (VEGF) Trap group (1 μg/μL, 3 μL); fibroblast growth factor (FGF) Trap group (1 μg/μL, 3 μL). Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein (GFAP) expression was examined by immunofluorescence. Blood-retinal barrier (BRB) breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy (TEM). Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay (ELISA). The retinal expression of intercellular cell adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction (qPCR). RESULTS: TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap (all P

We study the properties of strange quark matter (SQM) and quark stars (QSs) in strong magnetic fields within the extended confined isospin-density-dependent mass (CIDDM) model including the temperature dependence of the equivalent mass for quarks. The quark symmetry energy, quark symmetry free energy, and the equation of state (EOS) of SQM in constant magnetic fields at finite temperature are investigated, and it is found that including the temperature dependence in CIDDM model and considering strong magnetic fields can both significantly influence the properties of the SQM and the maximum mass of quark stars. Using the density-dependent magnetic field and assuming two extreme cases for the magnetic field orientation in QSs (the radial orientation in which the local magnetic fields are along the radial direction and the transverse orientation in which the local magnetic fields are randomly oriented but perpendicular to the radial orientation), we analyze the mass-radius relations for different stages of the protoquark stars (PQSs) along the star evolution. Our results indicate that the maximum mass of magnetized PQSs may depend on not only the strength distribution and the orientation of the magnetic fields inside the PQSs, but also the heating process and the cooling process in the star evolution.

The flash vacuum pyrolysis (FVP) technique is useful for preparing curved polycyclic aromatic compounds (PAHs) and caged nanocarbon molecules, such as the well-known corannulene and fullerene C60. However, the operating temperature of the traditional FVP apparatus is limited to ~1250 °C, which is not sufficient to overcome the high energy barriers of some reactions. Herein, we report an ultrahigh-temperature FVP (UT-FVP) apparatus with a controllable operating temperature of up to 2500 °C to synthesize fullerene C60 from a nonaromatic single carbon reactant, i.e., chloroform, at 1350 °C or above. Fullerene C60 cannot be obtained from CHCl3 using the traditional FVP apparatus because of the limitation of the reaction temperature. The significant improvements in the UT-FVP apparatus, compared to the traditional FVP apparatus, were the replacement of the quartz tube with a graphite tube and the direct heating of the graphite tube by impedance heating instead of indirect heating of the quartz tube using an electric furnace. Because of the higher temperature range, UT-FVP can not only synthesize fullerene C60 from single carbon nonaromatic reactants but sublimate some high-molecular-weight compounds to synthesize larger curved PAHs in the future.

For the Android platform malicious application,a method of mapping behavior to privilege characteristics by combining static privilege feature analysis and dynamic behavior analysis was proposed,and association analysis algorithm was used to dig out the association rules between privilege features.Feature as a naive Bayesian classification algorithm input,a malicious application detection model was established.Finally,the experiment verify the effectiveness and accuracy of the method.

Pepper (Capsicum spp.) is an important vegetable crop in the world. Now the pepper in China contributes one-third of the world's peppers production. Genetic diversity of the pepper germplasm of China is expected interesting to know. To explore the structure of genetic diversity in Chinese pepper germplasm resources and possible relationship with cultivar types or geographic origin, we sampled and compared 372 GenBank pepper accessions (local cultivars and landraces) from 31 provinces, autonomous regions and municipalities of China and 31 additional accessions from other countries. These accessions were genotyped using 28 simple sequence repeat (SSR) markers spanning the entire pepper genome. We then investigated the genetic structure of the sampled collection using model-based analysis in STRUCTURE v2.3.4 and examined genetic relationships by the unweighted pair-group method of mathematical averages (UPGMA) in MEGA. In addition to geographic origin, we evaluated eight plant and fruit traits. In total, 363 alleles were amplified using the 28 SSR primers. Gene diversity, polymorphism information content and heterozygosity of the 28 SSR loci were estimated as 0.09–0.92, 0.08–0.92 and 0.01–0.34, respectively. The UPGMA cluster analysis clearly distinguished Capsicum annuum L. from other cultivated pepper species. Population structure analysis of the 368 C. annuum accessions uncovered three genetic groups which also corresponded to distinct cultivar types with respect to the plant and fruit descriptors. The genetic structure was also related to the geographic origin of the landraces. Overall results indicate that genetic diversity of Chinese pepper landraces were structured by migration of genotypes followed by human selection for cultivar types in agreement with consumption modes and adaptation to the highly diversified agro-climatic conditions.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes to cancer progression through multiple processes of cancer development, which makes it an attractive target for cancer therapy. The IL-6/STAT3 pathway is associated with an advanced stage in colorectal cancer patients. In this study, we identified trichothecin (TCN) as a novel STAT3 inhibitor. TCN was found to bind to the SH2 domain of STAT3 and inhibit STAT3 activation and dimerization, thereby blocking STAT3 nuclear translocation and transcriptional activity. TCN did not affect phosphorylation levels of STAT1. TCN significantly inhibited cell growth, arrested cell cycle at the G0/G1 phase, and induced apoptosis in HCT 116 cells. In addition, the capacities of colony formation, migration, and invasion of HCT 116 cells were impaired upon exposure to TCN with or without IL-6 stimulation. In addition, TCN treatment abolished the tube formation of HUVEC cells in vitro. Taken together, these results highlight that TCN inhibits various cancer-related features in colorectal cancer development in vitro by targeting STAT3, indicating that TCN is a promising STAT3 inhibitor that deserves further exploration in the future.

AIM:To identify the genetic defects in a Chinese family with achromatopsia.METHODS:A 2.5-year-old boy, who displayed nystagmus, photophobia, and hyperopia since early infancy, was clinically evaluated. To further confirm and localize the causative mutations in this family, targeted region capture and next-generation sequencing of candidate genes, such as CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H were performed using a custom-made capture array.RESULTS:Slit-lamp examination showed no specific findings in the anterior segments. The optic discs and maculae were normal on fundoscopy. The unaffected family members reported no ocular complaints. Clinical signs and symptoms were consistent with a clinical impression of autosomal recessive achromatopsia. The results of sequence analysis revealed two novel missense mutations in CNGA3, c.633T>A (p.D211E) and c.1006G>T (p.V336F), with an autosomal recessive mode of inheritance.CONCLUSION: Genetic analysis of a Chinese family confirmed the clinical diagnosis of achromatopsia. Two novel mutations were identified in CNGA3, which extended the mutation spectrum of this disorder.

AIM:To determine the effects of rapamycin on experimental autoimmune uveoretinitis (EAU) and investigate of role of rapamycin on T cell subsets in the disease. METHODS:EAU was induced in rats using peptides 1169 to 1191 of the interphotoreceptor binding protein (IRBP). Rapamycin (0.2 mg/kg/d) was administrated by intraperitoneal injection for a consecutive 7d after immunization. Th1/Th2/Th17 cytokines, TGF-β1, and IL-6 produced by lymphocyteswere measured by ELISA, while Th17 cells and CD4+CD25+ regulatory T cells (Tregs) from rat spleen were detected by flow cytometry. RESULTS: Intraperitoneal treatment immediately after immunization dramatically ameliorated the clinical course of EAU. Clinical responses were associated with reduced retinal inflammatory cell infiltration and tissue destruction. Rapamycin induced suppression of Th1/Th2/Th17 cytokines, including IFN-γ, IL-2, IL-17, IL-4, and IL-10 release from T lymphocytes of EAU rats, in vitro. Rapamycin also significantly increased TGF-β1 production but had no effect on IL-6 productionof T lymphocytes from EAU rats in vitro. Furthermore, rapamycin decreased the ratio of Th17 cells/CD4+T cells and upregulated Tregs in EAU, as detected by flow cytometry. CONCLUSION: Rapamycin effectively interferes with T cell mediated autoimmune uveitis by inhibiting antigen-specific T cell functions and enhancing Tregs in EAU. Rapamycin is a promising new alternative as an adjunct corticosteroid-sparing agent for treating uveitis.

Background: Spinal anesthesia was considered as a reasonable anesthetic option in severe preeclampsia when cesarean delivery is indicated, and there is no indwelling epidural catheter or contraindication to spinal anesthesia. However, the ideal dose of intrathecal bupivacaine has not been quantified for cesarean delivery for severe preeclamptic patients. This study aimed to determine the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery. Methods: Two hundred severely preeclamptic patients are undergoing elective cesarean delivery under combined spinal-epidural anesthesia enrolled in this randomized, double-blinded, dose-ranging study. Patients received 4 mg, 6 mg, 8 mg, or 10 mg intrathecal hyperbaric bupivacaine with 2.5 μg sufentanil. Successful spinal anesthesia was defined as a T6 sensory level achieved within 10 minutes after intrathecal drug administration and/or no epidural supplement was required during the cesarean section. The ED 50 and ED 95 were calculated with a logistic regression model. Results: ED 50 and ED 95 of intrathecal bupivacaine for successful spinal anesthesia were 5.67 mg (95% confidence interval [CI]: 5.20-6.10 mg) and 8.82 mg (95% CI: 8.14-9.87 mg) respectively. The incidence of hypotension in Group 8 mg and Group 10 mg was higher than that in Group 4 mg and Group 6 mg (P < 0.05). The sensory block was significantly different among groups 10 minutes after intrathecal injection (P < 0.05). The use of lidocaine in Group 4 mg was higher than that in other groups (P < 0.05). The use of phenylephrine in Group 8 mg and Group 10 mg was higher than that in the other two groups (P < 0.05). The lowest systolic blood pressure before the infant delivery of Group 8 mg and Group 10 mg was lower than the other two groups (P < 0.05). The satisfaction of muscle relaxation in Group 4 mg was lower than other groups (P < 0.05). There was no significant difference in patients′ satisfaction and the newborns′ Apgar score and the blood gas analysis of umbilical artery serum (P > 0.05). Conclusion: Our study showed that the ED 50 and ED 95 of intrathecal bupivacaine for severely preeclamptic patients undergoing elective cesarean delivery were 5.67 mg and 8.82 mg, respectively. In addition, decreasing the dose of intrathecal bupivacaine could reduce the incidence of maternal hypotension.

Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. Recent studies have shown that MCT4 is over-expressed in various cancers; however, its role in cancer maintenance and aggressiveness has not been fully demonstrated. This study investigated the role of MCT4 in oral squamous cell carcinoma (OSCC), and found that it is highly expressed in OSCC patients by using immunohistochemistry. Moreover, this over-expression of MCT4 was closely associated with tumor size, TNM classification, lymphatic metastasis, distant metastasis and tumor recurrence, and also poor prognosis. To further study mechanisms of MCT4 in vitro, we used small-interfering RNA to silence its expression in OSCC cell lines. The results showed that knock-down of MCT4 decreased cell proliferation, migration, and invasion. The inhibition of proliferation was associated with down-regulation of p-AKT and p-ERK1/2, while decreased cell migration and invasion may be caused by down-regulation of integrin β4-SRC-FAK and MEK-ERK signaling. Together, these findings provide new insight into the critical role of MCT4 in cell proliferation and metastasis in OSCC.

Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα) restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA), overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways.

The title compound, C11H13N5, is a Schiff base synthesized by the reaction of 4-amino-4H-1,2,4-triazole and 4-(dimethylamino)benzaldehyde. The dihedral angle between the benzene and triazole rings is 43.09 (11)°. The crystal structure displays weak C—H...N interactions.

Since the antiretroviral therapy (ART) was introduced to patients infected by human immunodeficiency virus (HIV), the HIV related mortality and morbidity have been significantly reduced. The major obstacle for long-term successful anti-HIV treatment is the emergence of drug resistant mutants. Current data of drug resistance was mainly obtained on HIV-1 subtype B but rarely on non-B virus, even more rare with newly emerged circulating recombinant forms (CRFs). The lack of such data limits the rational management of ART for the increasing number of patients infected by non-subtype B virus. In this study, a HIV-1 CRF07_BC strain CNGZD was isolated from a HIV patient and its genome was sequenced and deposited in GenBank (JQ423923). Potential drug resistant mutants of this CRF07_BC virus strain were selected in PBMCs cultures in the presence of Nevirapine (NVP), which is the most frequently used antiretroviral drug in China. Four combination profiles of mutations were identified in the NVP-selected mutants, which were initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two other mutations at the end of the selections, respectively. A total of seven previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N) and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the reverse transcriptase gene were found in these NVP-selected mutants. Phenotypic analysis in the NVP-selected mutants showed that all the mutations, except P4H, contribute to NVP resistance. Among them, V106M and Y181C reduce NVP susceptibility for more than 20-fold, while the other mutations cause less than 20 folds drug resistance. Although the information obtained in this in vitro selection study may not fully cover resistant mutations which will actually occur in patients, it has still provided useful information for rational management of ART in patients infected with HIV CRF_BC subtype.

Zinc distributes widely in the central nervous system, especially in the hippocampus, amygdala and cortex. The dynamic balance of zinc is critical for neuronal functions. Zinc modulates the activity of N-methyl-D-aspartate receptors (NMDARs) through the direct inhibition and various intracellular signaling pathways. Abnormal NMDAR activities have been implicated in the aetiology of many brain diseases. Sustained zinc accumulation in the extracellular fluid is known to link to pathological conditions. However, the mechanism linking this chronic zinc exposure and NMDAR dysfunction is poorly understood.We reported that chronic zinc exposure reduced the numbers of NR1 and NR2A clusters in cultured hippocampal pyramidal neurons. Whole-cell and synaptic NR2A-mediated currents also decreased. By contrast, zinc did not affect NR2B, suggesting that chronic zinc exposure specifically influences NR2A-containg NMDARs. Surface biotinylation indicated that zinc exposure attenuated the membrane expression of NR1 and NR2A, which might arise from to the dissociation of the NR2A-PSD-95-Src complex.Chronic zinc exposure perturbs the interaction of NR2A to PSD-95 and causes the disorder of NMDARs in hippocampal neurons, suggesting a novel action of zinc distinct from its acute effects on NMDAR activity.

The title compound, C6H8N4O3·2H2O, which crystallized as a dihydrate, has two almost planar segments viz. the pyrimidine ring and the C—N—C(=O)—C group [maxmum deviations of 0.020 (2) and 0.014 (2) Å, respectively], with a dihedral angle of 87.45°. In the crystal, the components are linked by O—H...O and N—H...O hydrogen bonds.

In order to improve the oxidative desulfurization (ODS) performance of MOF materials, an effective way is to convert a microporous MOF into a hierarchical porous MOF (HP-MOF) by utilizing the linker selective retention strategy. Herein, UiO-66 with the introduction of an unstable linker ligand (dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, dhtz) can selectively remove dhtz ligands to form HP-MOF (HP-UiO-66-dhtz) through heat treatment at high temperature. While maintaining the original structure of UiO-66, HP-UiO-66-dhtz features mesopores and abundant Lewis acid sites, showing excellent ODS performance for diphenylthiophene (DBT). [ABSTRACT FROM AUTHOR]