Mitochondrial VOLTAGE-DEPENDENT ANION CHANNEL 3 regulates stomatal closure by abscisic acid signaling.

In Arabidopsis (Arabidopsis thaliana), stomatal closure mediated by abscisic acid (ABA) is redundantly controlled by ABA receptor family proteins (PYRABACTIN RESISTANCE 1 [PYR1]/PYR1-LIKE [PYLs]) and subclass III SUCROSE NONFERMENTING 1 (SNF1)-RELATED PROTEIN KINASES 2 (SnRK2s). Among these proteins, the roles of PYR1, PYL2, and SnRK2.6 are more dominant. A recent discovery showed that ABA-induced accumulation of reactive oxygen species (ROS) in mitochondria promotes stomatal closure. By analyzing stomatal movements in an array of single and higher order mutants, we revealed that the mitochondrial protein VOLTAGE-DEPENDENT ANION CHANNEL 3 (VDAC3) jointly regulates ABA-mediated stomatal closure with a specialized set of PYLs and SnRK2s by affecting cellular and mitochondrial ROS accumulation. VDAC3 interacted with 9 PYLs and all 3 subclass III SnRK2s. Single mutation in VDAC3, PYLs (except PYR1 and PYL2), or SnRK2.2/2.3 had little effect on ABA-mediated stomatal closure. However, knocking out PYR1, PYL1/2/4/8, or SnRK2.2/2.3 in vdac3 mutants resulted in significantly delayed or attenuated ABA-mediated stomatal closure, despite the presence of other PYLs or SnRK2s conferring redundant functions. We found that cellular and mitochondrial accumulation of ROS induced by ABA was altered in vdac3pyl1 mutants. Moreover, H2O2 treatment restored ABA-induced stomatal closure in mutants with decreased stomatal sensitivity to ABA. Our work reveals that VDAC3 ensures redundant control of ABA-mediated stomatal closure by canonical ABA signaling components.

RNF20/RNF40 ameliorates streptozotocin-induced type 1 diabetes by activating vitamin D receptors in vivo.

BACKGROUND: Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. METHODS: In this study, streptozotocin (STZ)-induced mice type 1 diabetes model was used. The protein expressions of genes were examined through Western blot analysis. Fasting blood glucose was detected through glucose meter. The plasma insulin was tested through the commercial kit. Hematoxylin and eosin staining was utilized to observe pathological changes of pancreatic tissues. Immunofluorescence assay was performed to evaluate the level of insulin. The levels of pro-inflammatory cytokines in serum were assessed by enzyme-linked-immunosorbent serologic assay. The cell apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labelling assay. RESULTS: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40. Besides, the VDR expression was positively regulated by RNF20/RNF40. Finally, VDR knockdown reversed improved hyperglycemia, inflammation, and cell apoptosis stimulated by overexpression of RNF20/RNF40. CONCLUSION: Our findings proved that RNF20/RNF40 activated VDR to relieve type 1 diabetes. This work might highlight the functioning of RNF20/RNF40 in the treatment of type 1 diabetes.

The Challenge and Opportunity of NTRK Inhibitors in Non-Small Cell Lung Cancer.

With the development of targeted therapy, non-small cell lung cancer (NSCLC) patients could have more treatment choices if target mutation presents. The neurotrophic tropomyosin receptor kinase (NTRK) has a low prevalence in NSCLC, roughly around 0.5%. FDA had approved two first generation NTRK inhibitors, larotrectinib and entrectinib. Both medications have excellent CNS penetration. This manuscript will review available data on targeting NTRK fusions in NSCLC and mechanisms of drug resistance.

Vascular Endothelial Growth Factor expression in peripheral blood of patients with pregnancy induced hypertension syndrome and its clinical significance.

OBJECTIVE: This study was conducted was to detect vascular endothelial growth factor (VEGF) levels in peripheral blood of patients with pregnancy-induced hypertension (PIH) syndrome and to investigate VEGF correlation with PIH occurrence. METHODS: Double-antibody enzyme-linked immunosorbent assay and fluorescent quantitative polymerase chain reaction were used to detect VEGF levels in the peripheral blood of non-pregnant women (normal group, 30 cases), normal pregnant women (pregnancy group, 30 cases) and PIH patients (PIH group, 30 cases). RESULTS: VEGF level in the pregnancy group was significantly higher than in the normal group, and the difference between these two groups was significant (P < 0.001). In the pregnancy group, VEGF reached the maximum level at the metaphase stage of pregnancy and started to decrease at advanced pregnancy. VEGF level in the PIH group was significantly lower than in the pregnancy group at advanced pregnancy (P < 0.01), and VEGF level significantly and gradually decreased with PIH aggravation (P < 0.05). CONCLUSIONS: The significant decrease of VEGF level after pregnancy was possibly an important factor of PIH pathogenesis.

Evaluating the adoption of irrigation technology in a well-irrigated winter wheat－summer maize cropping system.

Determining suitable irrigation technology is of paramount for promoting water-saving agriculture, particularly for winter wheat-summer maize rotation system in well-irrigated regions. To optimize and assess the efficacy of various irrigation technologies (specifically, semi-fixed sprinkler irrigation, walking sprinkler, semi-automatic buried telescopic sprinkler irrigation, thin-soft spray tape irrigation, drip irrigation, self-driven winch sprinkler and manually moving spray gun irrigation, marked as A, B, C, D, E, F and G) applied in south central North China Plain, we first conducted an economic analysis for the winter wheat-summer maize rotation. Subsequently, employing a comprehensive set of 20 indicators spanning economic, societal, technological, ecological, and resource aspects, we employed a TOPSIS model with integrative weighting approach using "AHP + Entropy". We also employed principal component analysis and the Sankey diagram method to explore characteristics of different irrigation techniques and indexes. Irrigation mode E, conserving energy by 63.19% compared to mode B and offering labor savings five times greater than the mode D. The highest economic benefit for the rotation system was observed with the mode C, resulting in a 25.26% increase compared to the mode G. The top three irrigation modes based on scores were D, G, and E, with scores of 0.532, 0.490, and 0.474, respectively. The Sankey diagram revealed distinct preferences among different agricultural entities for specific irrigation modes. For specific stakeholders, we recommend irrigation modes D, G, F, and B for small farmers, large and specialized family businesses, family farms, and farmer cooperatives, respectively. In conclusion, our findings provide valuable scientific support and recommendations for the practical application of irrigation technology in agricultural production.

Alteration of white matter microstructure in patients with sleep disorders after COVID-19 infection.

BACKGROUND: The pathophysiology of coronasomnia remains unclear. This study aimed to investigate changes in white matter (WM) microstructure and inflammatory factors in patients with sleep disorders (SD) characterized by poor sleep quantity, quality, or timing following coronavirus disease 2019 (COVID-19) infection in the acute phase (within one month) and whether these changes could be recovered at 3-month follow-up. METHODS: 29 acute COVID-19 patients with SD (COVID_SD) and 27 acute COVID-19 patients without SD (COVID_NonSD) underwent diffusion tensor imaging (DTI), tested peripheral blood inflammatory cytokines level, and measured Pittsburgh Sleep Quality Index (PSQI), and matched 30 uninfected healthy controls. Analyzed WM abnormalities between groups in acute phase and explored its changes in COVID_SD at 3-month follow-up by using tract-based spatial statistics (TBSS). Correlations between DTI and clinical data were examined using Spearman partial correlation analysis. RESULTS: Both COVID_SD and COVID_NonSD exhibited widespread WM microstructure abnormalities. The COVID_SD group showed specific WM microstructure changes in right inferior fronto-occipital fasciculus (IFOF) (lower fractional anisotropy [FA]/axial diffusivity [AD] and higher radial diffusivity [RD]) and left corticospinal tract (CST) (higher FA and lower RD) and higher interleukin-1ß (IL-1ß) compared with COVID_NonSD group. These WM abnormalities and IL-1ß levels were correlated PSQI score. After 3 months, the IFOF integrity and IL-1ß levels tended to return to normal accompanied by symptom improvement in the COVID_SD relative to baseline. CONCLUSION: Abnormalities in right IFOF and left CST and elevated IL-1ß levels were important neurophenotypes correlated with COVID_SD, which might provide new insights into the pathogenesis of neuroinflammation in SD patients induced by COVID-19.

Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances: a 3-month longitudinal study.

ABSTRACT: Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections. Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019 (COVID-19). However, neuroimaging studies on sleep disturbances caused by COVID-19 are scarce, and existing studies have primarily focused on the long-term effects of the virus, with minimal acute phase data. As a result, little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19. To address this issue, we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection, and verified the results using 3-month follow-up data. A total of 26 COVID-19 patients with sleep disturbances (aged 51.5 ± 13.57 years, 8 women and 18 men), 27 COVID-19 patients without sleep disturbances (aged 47.33 ± 15.98 years, 9 women and 18 men), and 31 age-and gender-matched healthy controls (aged 49.19 ± 17.51 years, 9 women and 22 men) were included in this study. Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis. We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes. The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores. Additionally, we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls. The 3-month follow-up data revealed indices of altered cerebral structure (cortical thickness, cortical grey matter volume, and cortical surface area) in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection. These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Correlation of Nonalcoholic Fatty Liver Disease with Dietary Folate and Serum Folate in U.S. Adults: Cross-Sectional Analyses from National Health and Nutrition Examination Survey 2009-2018.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a global health problem, and dietary intervention is still considered one of the primary interventions. This study aimed to examine cross-sectional associations between dietary and serum levels of folate and NAFLD. Methods: We conducted a study of 7543 adults who participated in the National Health and Nutrition Examination Survey, 2009-2018. NAFLD status was determined by a fatty liver index (FLI) value ≥60. Multivariable logistic regression models were used to estimate associations between folate and NAFLD. Results: Almost half (45%) of the patients were classified as having NAFLD based on the FLI. In the fully adjusted model, participants in the highest quartile of dietary total folate and food folate were found to have a lower prevalence of NAFLD than those in the lowest quartile [odds ratio (OR)quartile 4 versus 1 = 0.582; 95% confidence interval (CI) = 0.350-0.968; and ORquartile 4 versus 1 = 0.737; 95% CI = 0.611-0.888, respectively], and the fourth quartile values of serum total folate and 5-methyl-tetrahydrofolate were significantly negatively associated with NAFLD prevalence (ORquartile 4 versus 1 = 0.664; 95% CI = 0.495-0.891; and ORquartile 4 versus 1 = 0.712; 95% CI = 0.532-0.954, respectively). Subgroup analyses revealed that this beneficial association was more significant in women (ORquartile 4 versus 1 = 0.526; 95% CI = 0.329-0.843; pinteraction < 0.001) than in men (ORquartile 4 versus 1 = 0.805; 95% CI = 0.546-1.186). Conclusions: Higher dietary folate intake and serum folate levels are associated with a lower NAFLD prevalence among U.S. adults and the trend is more pronounced among women, indicating opportunities for dietary NAFLD interventions.

BMP4 is insufficient to differentiate umbilical cord mesenchymal stem cells into germ cell-like cells in vitro.

OBJECTIVES: Mesenchymal stem cell (MSC)-based therapies are expected to restore the fertility of infertile patients. In addition to MSC-derived paracrine effects to improve reproductive function, the differentiation of MSCs into germ cell (GC)-like cells is still a promising method to repair the injured reproductive system. The aim of this study was to examine the effect and potential mechanism of BMP4 in inducing umbilical cord MSC (UcMSC) transdifferentiation into GC-like cells. MATERIAL AND METHODS: UcMSCs were isolated, cultured and identified by flow cytometry and multilineage differentiation assays. After induction with 12.5 ng/mL BMP4 for 21 days, UcMSCs were collected for further examination. Immunofluorescence was used to detect the expression of Prdm1 and Prdm14; RT-PCR and RNA sequencing were used to detect differential gene expression (DEGs). RESULTS: The morphology of UcMSCs became large and flat after treatment with BMP4; the expression of GC-related genes (OCT4, Prdm1, Ifitm3 and Stella) was significantly downregulated, and further immunofluorescence results also confirmed the significant downregulation of Prdm1 in UcMSCs with BMP4 induction, while the expression of Prdm14 was significantly upregulated. The results of RNA sequencing and further analysis revealed no explicit correlation between BMP4 induction and the differentiation of UcMSCs into GC-like cells based on the 662 screened DEGs in UcMSCs with or without BMP4 induction. CONCLUSIONS: The differentiation of MSCs into GC-like cells is rather complex, and BMP4 alone is insufficient to induce UcMSCs to differentiate into GC-like cells, regardless of protein level or gene expression level.

Genetic polymorphism analysis of killer cell immunoglobulin-like receptor genes in the Chinese Uygur population.

Human killer cell immunoglobulin-like receptors are expressed in natural killer cells and subsets of T lymphocytes. They regulate these cells upon interaction with human leukocyte antigen class I molecules and other ligands presented by target cells. KIR gene frequencies and haplotype distributions have been shown to differ significantly between populations from different geographical regions and ethnic origins, which relates to functional variations in the immune response. We have investigated KIR gene frequencies and genotype diversities of 15 KIR genes (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, ID, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in 120 unrelated healthy individuals of the Uygur population living in the Xinjiang autonomous region of China. All individuals were typed positive for the four framework loci KIR3DL3, 2DL4, 3DL2 and KIR3DP1, while activating genes (KIR2DS1, 2DS2, 2DS3, 2DS5 and KIR3DS1) indicated some variation in this population. KIR3DS1 was found in a higher frequency in the studied population than in other groups from China. Linkage disequilibrium among KIR genes displayed a wide range. χ(2) analysis, conducted among non-ubiquitous genes, based on the KIR gene frequency data from our study population and previously published population data, revealed significant differences in the KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 genes. A neighbor-joining phylogenic tree, built using the observed carrier frequencies data of 13 KIR loci (KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 3DL1, 3DL2, 3DL3, 2DS1, 2DS2, 2DS3, 2DS5, and 3DS1), showed relationships between the population studied and other previously reported populations. The present study can therefore be valuable for enriching the ethnical gene information resources of the KIR gene pool, for population origin studies and for KIR-related clinical practice.

Genetic data provided by 21 autosomal STR loci from Chinese Tujia ethnic group.

The aim of this study was to investigate allelic frequency distribution and forensic genetic parameters of autosomal short tandem repeats (STR) loci of the population samples from 107 Tujia individuals from Chinese Hubei Province. Twenty-one autosomal STR genetic markers (D9S1122, D6S474, D6S1017, D5S2500, D4S2408, D3S4529, D2S441, D2S1776, D22S1045, D20S482, D1S1677, D1S1627, D1GATA113, D19S433, D18S853, D17S1301, D11S4463, D12ATA63, D10S1248, D10S1435 and D14S1434) were simultaneously amplified in a new multiplex polymerase chain reaction system. 155 alleles for all the STR loci from the Tujia population were observed and the corresponding allelic frequencies ranged from 0.005 to 0.589. Expected heterozygosity, polymorphic information content, power of discrimination and power of exclusion of the 21 STR loci in the Tujia population were from 0.579 to 0.824, from 0.525 to 0.802, from 0.773 to 0.945 and from 0.257 to 0.641, respectively. Our results indicate that the autosomal STRs multiplex system provides highly informative STR data and could be useful in forensic individual identification and parentage testing in this region.

Identification and validation of a prognostic signature related to hypoxic tumor microenvironment in cervical cancer.

BACKGROUND: Hypoxia is a common microenvironment condition in most malignant tumors and has been shown to be associated with adverse outcomes of cervical cancer patients. In this study, we investigated the effects of hypoxia-related genes on tumor progress to characterize the tumor hypoxic microenvironment. METHODS: We retrieved a set of hypoxia-related genes from the Molecular Signatures Database and evaluated their prognostic value for cervical cancer. A hypoxia-based prognostic signature for cervical cancer was then developed and validated using tumor samples from two independent cohorts (TCGA-CESC and CGCI-HTMCP-CC cohorts). Finally, we validated the hypoxia prediction of ccHPS score in eight human cervical cancer cell lines treated with the hypoxic and normoxic conditions, and 286 tumor samples with hypoxic category (more or less) from Gene Expression Omnibus (GEO) database with accession GSE72723. RESULTS: A risk signature model containing nine hypoxia-related genes was developed and validated in cervical cancer. Further analysis showed that this risk model could be an independent prognosis factor of cervical cancer, which reflects the condition of the hypoxic tumor microenvironment and its remodeling of cell metabolism and tumor immunity. Furthermore, a nomogram integrating the novel risk model and lymphovascular invasion status was developed, accurately predicting the 1-, 3- and 5-year prognosis with AUC values of 0.928, 0.916 and 0.831, respectively. These findings provided a better understanding of the hypoxic tumor microenvironment in cervical cancer and insights into potential new therapeutic strategies in improving cancer therapy.

Menstrual blood-derived endometrial stem cells ameliorate the viability of ovarian granulosa cells injured by cisplatin through activating autophagy.

Although the cancer incidence showed a yearly increasing trend, the long-term survival rate of cancer patients significantly increased with the continuous improvements in cancer diagnosis and treatment. Therefore, recent strategies for cancer treatment not only focus on improving the survival rate of patients but also simultaneously consider the life quality of cancer patients, especially for those with fertility requirements. Stem cell-based therapies have exhibited promising improvement in various disease treatments, and provide hope for diseases without effective treatment. Menstrual blood-derived endometrial stem cells (MenSCs) can be noninvasively and periodically obtained from discarded menstrual blood samples and exhibit high proliferative capacity, low immunogenicity and autologous transplantation. As expected, MenSCs treatment effectively improved the viability of cisplatin-injured ovarian granulosa cells (GCs) and significantly upregulated their antiapoptotic capacity. Further results demonstrated that MenSCs treatment significantly upregulated autophagy activity in cisplatin-injured ovarian GCs, and the degree of autophagy activation was positively correlated with the viability improvement of ovarian GCs, while autophagy inhibitors significantly impaired MenSC-promoted viability improvement of cisplatin-injured ovarian GCs. Additionally, MenSCs treatment can also significantly promote the proliferation of normal GCs by activating the PI3K/Akt signaling pathway. Conclusively, MenSCs treatment not only enhanced the antiapoptotic capacity and survival of cisplatin-injured ovarian GCs by upregulating autophagy activity but also improved the viability of normal ovarian GCs by activating the PI3K/Akt signal pathway. These results provide a theoretical and experimental foundation for the clinical application of MenSCs in improving chemotherapy-induced ovarian injury and delaying ovarian senescence.

Aquaporin-3 in keratinocytes and skin: its role and interaction with phospholipase D2.

Aquaporin 3 (AQP3) is an aquaglyceroporin that transports water and glycerol and is expressed in the epidermis, among other epithelial tissues. We have recently shown that there is an association between this glycerol channel and phospholipase D2 (PLD2) in caveolin-rich membrane microdomains. While PLD2 is able to hydrolyze membrane phospholipids to generate phosphatidic acid, this enzyme also catalyzes, in the presence of primary alcohols, a transphosphatidylation reaction to produce a phosphatidylalcohol. We have proposed that AQP3 associated with PLD2 provides the physiological primary alcohol glycerol to PLD2 for use in the transphosphatidylation reaction to generate phosphatidylglycerol (PG). Further, we have proposed that PG functions as a signaling molecule to mediate early epidermal keratinocyte differentiation, and manipulation of this signaling module inhibits keratinocyte proliferation and enhances differentiation. In contrast, other investigators have suggested a proliferative role for AQP3 in keratinocytes. In addition, AQP3 knockout mice exhibit an epidermal phenotype, characterized by dry skin, decreased elasticity and delayed barrier repair and wound healing, which can be corrected by glycerol but not other humectants. AQP3 levels have also been found to be altered in human skin diseases. In this article the evidence supporting a role for AQP3 in the epidermis will be discussed.

Caspase 9 gene polymorphism and susceptibility to lumbar disc disease in the Han population in northern China.

Many studies have demonstrated that apoptosis is involved in the development of disc degeneration. The initiator caspase 9 is activated through the apoptosome-driven intrinsic apoptotic pathway. The present study aimed to assess the potential association between the caspase 9 gene polymorphism and lumbar disc herniation (LDH) susceptibility, as well as severe grades of disc degeneration in the Han population in northern China. Genotyping was performed using the polymerase chain reaction and polymorphism was analyzed by restriction endonuclease cleavage in 387 patients with LDH and 412 control subjects. The allelic frequencies of caspase 9 Ex5+32 A were 0.483 and 0.391 in case patients and control subjects, respectively. Compared to those with the AA genotype, subjects with the GA/GG genotype have a higher risk to develop LDH (odds ratio 1.91; 95% confidence interval 1.29-2.81). Moreover, the GA/GG genotype was found to contribute to the risk of more severe grades of disc degeneration, as observed in magnetic resonance imaging scan. In conclusion, this study suggests that the single nucleotide polymorphism in the caspase 9 Ex5 + 32 G/A may be associated with LDH and disc degeneration in the Han population of northern China.

Genetic diversities of 21 non-CODIS autosomal STRs of a Chinese Tibetan ethnic minority group in Lhasa.

In the present study, we investigated 21 short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045, D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433, D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435, D5S2500), which are not included in the Combined DNA Index System and Amelogenin locus in 104 randomly selected healthy autochthonous individuals from the Tibetan ethnic minority group residing in the Lhasa region, Tibet Autonomous Region of China. Allelic frequencies, common forensic statistical parameters, and the Hardy-Weinberg equilibrium in this population were calculated with a modified PowerState V12.xls. A total of 143 alleles were found in the Tibetan group with corresponding allelic frequencies ranging from 0.005 to 0.582. The observed heterozygosity, the expected heterozygosity, the power of discrimination, the power of exclusion, and the polymorphic information content ranged from 0.615 to 0.817, 0.559 to 0.787, 0.727 to 0.926, 0.310 to 0.632, and 0.488 to 0.760, respectively. Chi-square tests of the observed genotype frequencies and expected genotype frequencies in the samples showed no departure from the Hardy-Weinberg equilibrium at all loci except for D5S2500. Our results demonstrate that these 21 STRs are highly polymorphic and suitable for anthropological research, population genetics, and forensic paternity testing and human individual identification in this region, and can enrich Chinese ethnical genetic informational resources.

Label-free detection of nucleic acids by turn-on and turn-off G-quadruplex-mediated fluorescence.

In this study we have used two fluorescent probes, tetrakis(diisopropylguanidino)-zinc-phthalocyanine (Zn-DIGP) and N-methylmesoporphyrin IX (NMM), to monitor the reassembly of "split" G-quadruplex probes on hybridization with an arbitrary "target" DNA. According to this approach, each split probe is designed to contain half of a G-quadruplex-forming sequence fused to a variable sequence that is complementary to the target DNA. Upon mixing the individual components, both base-pairing interactions and G-quadruplex fragment reassembly result in a duplex-quadruplex three-way junction that can bind to fluorescent dyes in a G-quadruplex-specific way. The overall fluorescence intensities of the resulting complexes were dependent on the formation of proper base-pairing interactions in the duplex regions, and on the exact identity of the fluorescent probe. Compared with samples lacking any "target" DNA, the fluorescence intensities of Zn-DIGP-containing samples were lower, and the fluorescence intensities of NMM-containing samples were higher on addition of the target DNA. The resulting biosensors based on Zn-DIGP are therefore termed "turn-off" whereas the biosensors containing NMM are defined as "turn-on". Both of these biosensors can detect target DNAs with a limit of detection in the nanomolar range, and can discriminate mismatched from perfectly matched target DNAs. In contrast with previous biosensors based on the peroxidase activity of heme-bound split G-quadruplex probes, the use of fluorescent dyes eliminates the need for unstable sensing components (H(2)O(2), hemin, and ABTS). Our approach is direct, easy to conduct, and fully compatible with the detection of specific DNA sequences in biological fluids. Having two different types of probe was highly valuable in the context of applied studies, because Zn-DIGP was found to be compatible with samples containing both serum and urine whereas NMM was compatible with urine, but not with serum-containing samples.

Genetic polymorphism analysis of 15 STR loci in Chinese Hui ethnic group residing in Qinghai province of China.

In the present study, we investigated the diversity distributions of allelic frequencies of 15 short tandem repeats (STRs) loci in a sample of Chinese Hui ethnic group in the Ningxia Hui Autonomous Region. The allelic frequencies of the 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were obtained from 2975 unrelated healthy Hui individuals. The STR genotyping data of all the samples were generated by DNA extraction, multiple amplification, GeneScan and genotype analysis. The genetic distances among different populations were calculated by using Nei's method and a phylogenetic tree was constructed based on the allelic frequencies of the same 15 STR loci using the neighbor-joining method. A total of 185 alleles were observed in the Hui population, with the corresponding allelic frequencies ranging from 0.0002 to 0.5322. Chi-Square tests showed that all STR loci were in Hardy-Weinberg equilibrium. The forensic statistical parameters of all the loci showed high values. The population data in this study were compared with the previously published population data from other ethnics or areas. The Hui population showed significant differences from the Minnan Han, Uigur, Ewenki, Yi, Tibetan, Maonan and Malay ethnic minority groups in some loci, and from the South Morocco population and the Moroccan population in all the loci. Our results are valuable for human individual identification and paternity testing in the Chinese Hui population and are expected to enrich the genetic information resources of Chinese populations.

Protective Effect of Shexiang Baoxin Pill on Myocardial Ischemia/Reperfusion Injury in Patients With STEMI.

Background: There is no definite effect in the treatment of myocardial ischemia/reperfusion (I/R) injury in patients with acute ST-segment elevation myocardial infarction (STEMI). We evaluated the protective effect of Shexiang Baoxin Pill (SBP) on I/R injury in STEMI patients. Methods: STEMI patients were randomly divided into a primary percutaneous coronary intervention (PPCI) group (n = 52) and a PPCI + SBP group (n = 51). The area at risk of infarction (AAR) and final infarct size (FIS) were examined by single-photon emission computed tomography (SPECT). I/R injury was assessed using myocardial salvage (MS) and salvage index (SI) calculated from AAR and FIS. Results: The ST-segment resolution (STR) in the PPCI + SBP group was significantly higher than that in the PPCI group (p = 0.036), and the peak value of high-sensitivity troponin T (hsTNT) was lower than that in the PPCI group (p = 0.048). FIS in the PPCI + SBP group was smaller than that in the PPCI group (p = 0.047). MS (p = 0.023) and SI (p = 0.006) in the PPCI + SBP group were larger than those in the PPCI group. The left ventricular ejection fraction (LVEF) in the PPCI + SBP group was higher than that in the PPCI group (p = 0.049), and N-terminal pro-B type natriuretic peptide (NT-proBNP) level in the PPCI + SBP group was lower than that in the PPCI group (p = 0.048). Conclusions: SBP can alleviate I/R injury (MS and SI), decrease myocardial infarction area (peak value of hsTNT and FIS), and improve myocardial reperfusion (MBG and STR) and cardiac function (LVEF and NT-proBNP).

Successful Treatment of Pembrolizumab-Induced Severe Capillary Leak Syndrome and Lymphatic Capillary Dysfunction.

Although capillary leak syndrome has a high mortality rate, its trigger, diagnosis, and treatment remain a challenge to clinicians because of the poor understanding of its mechanism and lack of treatment guidelines. With the extended use of immune checkpoint inhibitors in modern oncology, immune checkpoint inhibitor-associated immune-related adverse events have also expanded. We present a case of pembrolizumab-induced capillary leak syndrome and lymphatic capillary dysfunction in which the patient had an excellent clinical response to a tailored treatment strategy.