High-Q two-dimensional perovskite topological laser.

Quasi-two-dimensional perovskites have attracted widespread interest in developing low-cost high-quality small lasers. The nano cavity based on topologically protected valley edge states can be robust against special defects. Here, we report a high-quality two-dimensional perovskite topological photonic crystal laser based on the quantum valley Hall effect. By adjusting the position of the air holes relative to the pillar, radiation leakage in topological edge states is reduced to a large extent, electric field distribution becomes more uniform and the quality factor can be as high as 3.6 × 104. Our findings could provide opportunities for the development of high-power, stable perovskite lasers with topological protection.

Human Leukocyte Antigen Polymorphism HLA-A*24:02 is Associated with Acute Liver Disease in HBV-Infected Han Chinese Adults.

BACKGROUND: Whether polymorphic Human Leukocyte Antigen (HLA)-A, HLA-B and HLA-DRB1 alleles were associated with acute liver disease after hepatitis B virus (HBV) infections was investigated. METHODS: In this study, from initially 100 participants in each group, HLA-A, HLA-B and HLA-DRB1 sequences were available from 86 acute hepatitis B (AHB) patients and from 84 HBV-resistant individuals (controls), using sequencing-based typing allele groups and alleles that exhibited differences in distribution between the case and control groups were subjected to chi-squared and logistic regression analyses to identify those associated with AHB. A dose response analysis was also performed on the effect of HLA-A*24:02 allele number on acute liver disease following HBV infection. RESULTS: The frequency distribution of HLA-B and HLA-DRB1 alleles in the control group were in Hardy-Weinberg Equilibrium (P > .05). HLA-A*24:02 (χ2 = 6.949, P = .008) occurred most frequently in the AHB and HLA-DRB1*12:02 (χ2 = 7.768, P = .005) in the control group. With adjustment for sex, the logistic regression model showed that the HLA-A*24:02 allele was significantly associated with AHB liver injury (P = .0326, OR = 2.270, 95% CI: 1.070-4.816), whereas the other HLA-A, HLA-B, and HLA-DRB1 alleles were not (P > .05). A linear response was observed for the association between HLA-A*24:02 allele number and acute liver disease after HBV infections (χ2 = 4.428, P = .025). CONCLUSION: The HLA-A*24:02 allele may influence the severity of the cellular response to HBV infection, increasing the elimination of HBV-infected hepatocytes. The HLA-A*24:02 allele may be a potential screening marker for identifying people or regional populations in China at higher risk of acute liver disease following HBV infection.

Trending prevalence of healthcare-associated infections in a tertiary hospital in China during the COVID-19 pandemic.

BACKGROUND: The purpose of this study was to demonstrate both the four-year prevalence trend of healthcare-associated infections (HAIs) in a large tertiary hospital and the trend regarding the prevalence of HAIs following the outbreak of coronavirus disease 2019 (COVID-19) in order to provide evidence of hospital infection management during the COVID-19 pandemic. METHODS: Based on the hospital's electronic nosocomial infection databases related to HAIs, we retrospectively identified the HAI cases to assess the epidemiological characteristics of HAIs from January 1, 2018, to December 31, 2021, in a large tertiary hospital in China. Similarly, the trends of HAIs after the COVID-19 outbreak and the seasonal variation of HAIs were further analyzed. RESULTS: The HAI cases (n = 7833) were identified from the inpatients (n = 483,258) during the 4 years. The most frequently occurring underlying cause of HAIs was respiratory tract infections (44.47%), followed by bloodstream infections (11.59%), and urinary tract infections (8.69%). The annual prevalence of HAIs decreased from 2.39% in 2018 to 1.41% in 2021 (P = 0.032), with the overall prevalence of HAIs significantly decreasing since the outbreak of COVID-19 (2.20% in 2018-2019 vs. 1.44% in 2020-2021, P < 0.001). The prevalence of respiratory tract infections decreased most significantly; whereas, overall, the prevalence of HAIs was significantly greater during the winter compared with the rest of the year. CONCLUSIONS: Not only did the annual prevalence of HAIs decrease from 2018 to 2021, but it also significantly decreased since the start of the COVID-19 pandemic, particularly respiratory tract infections. These results provide evidence for the need to prevent HAIs, especially during the winter season.

The Effect of Multidimensional Nursing Intervention for Pain on Pain Levels in Patients with Lower Extremity Arteriosclerosis Obliterans.

Objective: This study aims to explore the effect of the multidimensional nursing intervention for pain on the pain level in patients with lower extremity arteriosclerosis obliterans. Methods: From January 2020 to April 2021, 132 patients with lower extremity arteriosclerosis obliterans in the First Affiliated Hospital of Xi'an Jiaotong University in China were enrolled in this prospective study. According to the random number table method, the patients were divided into the study group (n = 66; receiving multidimensional nursing intervention for pain) and the control group (n = 66; receiving routine nursing intervention). The pain level, sleep quality, and claudication distance were recorded before and after the intervention. The ankle brachial index before discharge and 1, 3 and 6 months after discharge was recorded. The getting out of bed time, length of hospital stay, satisfaction with pain control, and postoperative complications were also recorded. Results: The postoperative get out of bed time and hospital stay in patients in the study group were shorter than patients in the control group (P < .05). After the intervention, the pain level was lower and sleep quality higher in the study group than in the control group (P < .05), and the limp distance in the study group was longer (P < .05). Before discharge and at 1, 3 and 6 months after discharge, the ankle brachial index in the study group was higher than in the control group (P < .05). In addition, there were significant differences between the 2 groups (P < .05). Compared with the control group (10.606%), the incidence of postoperative complications in the study group (1.515%) was lower (P < .05). Conclusions: The multidimensional nursing intervention for pain may effectively reduce pain levels, improve sleep quality, increase claudication distance and improve satisfaction with pain control, thus improving patient prognosis.

Atropisomeric meroterpenoids with rare triketone-phloroglucinol-terpene hybrids from Baeckea frutescens.

Baefrutones A-F (1-6), six new meroterpenoids with rare triketone-phloroglucinol-monoterpene/sesquiterpene frameworks, together with their biosynthetically related intermediate (±)-baeckenon B (7), were isolated from the aerial part of Baeckea frutescens under the guidance of HPLC-Q/TOF-MS2 investigation. Compounds 1-4 represent the first examples of natural meroterpenoids existing as four pairs of inseparable diastereomeric atropisomers (2 : 1, 1H NMR integration) caused by the restricted rotation around the C-6-C-7-C-1' bonds arising from the intramolecular hydrogen bond between C-1 carbonyl and 2'-OH. The discovery of these architectures not only largely enriched the chemodiversity of the meroterpenoid and atropisomer library, but also might be exciting and challenging for asymmetric organic synthesis. Their structures and absolute configurations were established by extensive spectroscopic analysis, X-ray diffraction, and ECD calculations. Compounds 5 and 6 were biomimetically synthesized from 7 and ß-caryophyllene via a regioselective oxidative hetero-Diels-Alder reaction, thus providing access to the construction of the 6/6/9/4 tetracyclic ring system. The anti-inflammatory activities of these meroterpenoids were also discussed.

Human rotavirus strain Wa downregulates NHE1 and NHE6 expressions in rotavirus-infected Caco-2 cells.

Rotavirus (RV) is the most common cause of severe gastroenteritis and fatal dehydration in human infants and neonates of different species. However, the pathogenesis of rotavirus-induced diarrhea is poorly understood. Secretory diarrhea caused by rotavirus may lead to a combination of excessive secretion of fluid and electrolytes into the intestinal lumen. Fluid absorption in the small intestine is driven by Na+-coupled transport mechanisms at the luminal membrane, including Na+/H+ exchanger (NHE). Here, we performed qRT-PCR to detect the transcription of NHEs. Western blotting was employed for protein detection. Furthermore, immunocytochemistry was used to validate the NHE's protein expression. Finally, intracellular Ca2+ concentration was detected by confocal laser scanning microscopy. The results demonstrated that the NHE6 mRNA and protein expressed in the human colon adenocarcinoma cell line (Caco-2). Furthermore, RV-Wa induced decreased expression of the NHE1 and NHE6 in Caco-2 cell in a time-dependent manner. In addition, intracellular Ca2+ concentration in RV-Wa-infected Caco-2 cells was higher than that in the mock-infected cells. Furthermore, RV-Wa also can downregulate the expression of calmodulin (CaM) and calmodulin kinase II (CaMKII) in Caco-2 cells. These findings provides important insights into the mechanisms of rotavirus-induced diarrhea. Further studies on the underlying pathophysiological mechanisms that downregulate NHEs in RV-induced diarrhea are required.

[Development of an 18 X-InDel multiplex PCR system].

OBJECTIVE: To investigate Insertion/Deletion (InDel) polymorphism on the X chromosome and to screen 18 InDel loci for the Chinese Han population as a forensic DNA typing system auxiliary. METHODS: Eighteen X-InDel markers were selected using the Human Genome Browser and dbSNP database. Multiplex PCR primer pairs of selected X-InDel markers were designed using Primer 3 software and divided into 3 groups according to the amplified fragment length, labeled by FAM, HEX and TAMRA fluorescence dye, respectively. The population genetics research and comparative analysis of Chinese Han nationality and 4 main minorities, the Hui, Wei, Mongol, and Tibetan nationalities, were investigated with the system. RESULTS: A new multiplex genotyping system, named InDel X-18PLEX, was successfully developed and validated, consisted of 18 X-InDel markers on the X chromosome and 1 Amelogenin gender marker. No deviation from Hardy-Weinberg equilibrium expectations was detected in the distribution of genotypes in the 5 investigated ethnic groups. However, there was significant difference between their distributions. From the investigation of Han nationality, high female (0.9999994) and male (0.999 88) overall discrimination power values were obtained, as well as high overall mean exclusion chance values in trios (0.999 992) and in duos (0.99). CONCLUSION: InDel X-18PLEX meets the requirements as a forensic DNA complementary kit, providing effective supplementary analytical tools for difficult cases.

[Forensic application of 30 InDel loci in Han and She nationalities of Eastern China].

OBJECTIVE: To evaluate the forensic application value of 30 insertion/deletion (InDel) loci included in Investigator DIPplex Kit in Han and She nationalities of Eastern China. METHODS: A total of 565 unrelated individuals in Han nationality and 119 ones in She nationality of Eastern China were investigated using Investigator DIPplex Kit. Allele frequencies, population genetics parameters of the 30 InDel loci were statistically calculated. RESULTS: In Han nationality, the mean Ho was 0.413 3, the mean DP was 0.551 1, the mean PIC was 0.320 0. And in She nationality, the mean Ho was 0.389 6, the mean DP was 0.543 3, the mean PIC was 0.310 0. No deviation from Hardy-Weinberg equilibrium was observed in Han and She nationalities (P > 0.05). CONCLUSION: The 30 loci in Investigator DIPplex Kit show good genetic diversity in Han and She nationalities, and could be used as a supplemental tool for some special paternity cases.

Effective Prevention and Treatment of Acute Leukemias in Mice by Activation of Thermogenic Adipose Tissues.

Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are common hematological malignancies in adults. Despite considerable research advances, the development of standard therapies, supportive care, and prognosis for the majority of AML and ALL patients remains poor and the development of new effective therapy is urgently needed. Here, it is reported that activation of thermogenic adipose tissues (TATs) by cold exposure or ß3-adrenergic receptor agonists markedly alleviated the development and progression of AML and ALL in mouse leukemia models. TAT activation (TATA) monotherapy substantially reduces leukemic cells in bone marrow and peripheral blood, and suppresses leukemic cell invasion, including hepatomegaly and splenomegaly. Notably, TATA therapy prolongs the survivals of AML- and ALL-bearing mice. Surgical removal of thermogenic brown adipose tissue (BAT) or genetic deletion of uncoupling protein 1 (UCP1) largely abolishes the TATA-mediated anti-leukemia effects. Metabolomic pathway analysis demonstrates that glycolytic metabolism, which is essential for anabolic leukemic cell growth, is severely impaired in TATA-treated leukemic cells. Moreover, a combination of TATA therapy with chemotherapy produces enhanced anti-leukemic effects and reduces chemotoxicity. These data provide a new TATA-based therapeutic paradigm for the effective treatment of AML, ALL, and likely other types of hematological malignancies.

Long-term risk of overweight in offspring of Chinese women with gestational diabetes defined by IADPSG's but not by WHO's criteria.

AIMS: To examine long-term risk of overweight in offspring of women with gestational diabetes mellitus (GDM) defined by the International Association of Diabetes and Pregnancy Study Group (IADPSG)'s criteria but not by the 1999 World Health Organization (WHO)'s criteria. METHODS: We followed up 1681 mother-child pairs for 8 years in Tianjin, China. Overweight in children aged 1-5 and 6-8 were respectively defined as body mass index-for-age and -sex above the 2 z-score and 1 z-score curves of the WHO's child growth standards. Logistic regression was performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of hyperglycemia indices at oral glucose tolerance test and GDMs defined by different criteria for offspring overweight at different ages. RESULTS: Offspring of women with fasting plasma glucose ≥5.1 mmol/L were at increased risk of overweight at 6-8 years old (OR:1.45, 95% CI: 1.09-1.93). GDM defined by the IADPSG's criteria only was associated with increased risk of childhood overweight at 6-8 years old (1.65, 1.13-2.40), as compared with non-GDM by either of the two sets of criteria. CONCLUSIONS: Newly defined GDM by the IADPSG's criteria increased the risk of offspring overweight aged 6-8 years.

Development of the 16 X-STR loci typing system and genetic analysis in a Shanghai Han population from China.

This study developed a new multiplex PCR system that simultaneously amplifies 16 X-STR loci in the same PCR reaction, and the polymorphism and mutation rates of these 16 X-STR loci were explored in a Shanghai Han population from China. These loci included DXS10134, DXS10159, DXS6789, DXS6795, DXS6800, DXS6803, DXS6807, DXS6810, DXS7132, DXS7424, DXS8378, DXS9902, GATA165B12, GATA172D05, GATA31E08, and HPRTB. Samples from 591 unrelated individuals (293 males and 298 females) and 400 two-generation families were successfully analyzed using this multiplex system. Allele frequencies and mutation rates of the 16 loci were investigated, with the comparison of allele frequency distributions among different populations performed. Polymorphism information contents of these loci were all >0.6440 except the locus DXS6800 (0.4706). Nine cases of mutations were detected in the 16 loci from the investigation of 9232 meioses. Pairwise comparisons of allele frequency distributions showed significant differences for most loci among populations from different countries and ethnic groups but not among the Han population living in other areas of China. These results suggest that the 16 X-STR loci system provides highly informative polymorphic data for paternity testing and forensic identification in the Han population in Shanghai, China, as a complementary tool.

Genetic polymorphisms in 12 autosomal STRs in a Shanghai Han population from China.

In this study, a total of 484 unrelated healthy individuals and 359 two-generation families in the Han population in Shanghai, China were successfully analyzed with the Investigator HDplex Kit (Qiagen, Hilden, Germany). Hardy-Weinberg equilibrium tests demonstrated no significant deviation from expected values (p > 0.05) for the 12 autosomal STRs included in this kit. A total of 173 alleles were detected in 12 autosomal STR loci; the largest number of alleles (32) was detected for the SE33 locus. The combined power of discrimination was 0.99999999992. The combined mean exclusion chance in duo cases was 0.99982, whereas the combined mean exclusion chance in trio cases was 0.9999986. The average mutation rate across all loci was 0.0023 (95% confidence intervals: 0.0013-0.0039). These results suggest that the 12 autosomal STR loci can provide highly informative polymorphic data for paternity testing and forensic identification in the Han population in Shanghai, China.

Differences of DNA methylation profiles between monozygotic twins' blood samples.

Monozygotic twins (MZs) share an identical genomic sequence, which makes it impossible to discriminate one another with conventional genetic markers like STRs. On the other hand, phenotypic discordance between MZs implies the existence of different epigenetic characteristics. DNA methylation, an essential epigenetic modification, however, might be a potential biomarker to solve the forensic puzzle. In this study, we examined 22 pairs of MZs with a methylation BeadChip including 27,578 CpG sites. The results suggested that MZs exhibited remarkable differences of genome-wide 5-methylcytosine. According to a set of criteria of selection, 92 CpG sites with significant differences of methylation status within MZs were identified from the global epigenome. In conclusion, this pilot study suggested that CpG methylation profile could be a useful biomarker in individual identification of MZs.

[Progress in InDel as a new generation of genetic marker].

As forensic DNA typing experienced three generations of genetic marker researching stage, short tandem repeat (STR) has been widely used in forensic identification as a mature tool. Further exploration of the human genome led to the discovery of polymorphism markers of single nucleotide polymorphism (SNP) and Insertion/Deletion (InDel). InDel, which combines the desirable characteristics of previous genetic markers as a new type of genetic marker, has got extensive concern in fields like medical molecular biology and forensic biology. This paper generally reviews the history of research and the corresponding results of InDel along the line of time axis as well as the different aims of these research focusing on the progress in the multiple amplification system with several InDel as the genetic marker (autosomal or X chromosome) in forensic biology and anthropology. Finally, the direction of research in this field and the problems to be solved have been put forward.

Messenger RNA profiling for forensic body fluid identification: research and applications.

Identifying the origin of body fluids left at a crime scene can give a significant insight into crime scene reconstruction by supporting a link between sample donors and actual criminal acts. However, the conventional body fluid identification methods are prone to various limitations, such as time consumption, intensive labor, nonparallel manner, varying degrees of sensitivity and limited specificity. Recently, the analysis of cell-specific messenger RNA expression (mRNA profiling) has been proposed to supplant conventional methods for body fluid identification. Since 2011, the collaborative exercises have been organized by the European DNA Profiling Group (EDNAP) in order to evaluate the robustness and reproducibility of mRNA profiling for body fluid identification. The major advantages of mRNA profiling, compared to the conventional methods, include higher sensitivity, greater specificity, the ability of detecting several body fluids in one multiplex reaction, and compatibility with current DNA extraction and analysis procedure. In the current review, we provided an overview of the present knowledge and detection methodologies of mRNA profiling for forensic body fluid identification and discussed its possible practical application to forensic casework.

Fundamental roles of the Optineurin gene in the molecular pathology of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of motor neurons (MNs) in the brain and spinal cord. It is caused by multiple factors, including mutations in any one of several specific genes. Optineurin (OPTN) mutation is an essential cause of some familial and sporadic ALS. Besides, as a multifunctional protein, OPTN is highly expressed and conserved in the central nervous system. OPTN exerts its functions by interacting with various proteins, often acting as an adaptor to provide a link between two or more core proteins related to autophagy and inflammation, etc. OPTN mutation mainly results in its function deficiency, which alters these interactions, leading to functional impairment in many processes. Meanwhile, OPTN immunopositive inclusions are also confirmed in the cases of ALS due to C9ORF72, FUS, TARDBP, and SOD1 mutations. Therefore, OPTN gene may play fundamental roles in the molecular pathology of ALS in addition to OPTN mutation. In this review, we summarize the recent advances in the ALS pathology of OPTN defect, such as mitophagy disorder, neuroinflammation, neuronal axonal degeneration, vesicular transport dysfunction, etc., which will provide a reference for research on the pathogenesis and treatment of ALS.

Electrochemical sensors based on platinum-coated MOF-derived nickel-/N-doped carbon nanotubes (Pt/Ni/NCNTs) for sensitive nitrite detection.

As excess nitrite has a serious threat to the human health and environment, constructing novel electrochemical sensors for sensitive nitrite detection is of great importance. In this report, platinum nanoparticles were deposited on nickel-/N-doped carbon nanotubes, which were obtained through a self-catalytically grown process with Ni-MOF as precursors. The as-prepared Pt/Ni/NCNTs were applied as amperometric sensors and presented superior sensing properties for nitrite detection. Benefiting from the synergy of Pt and Ni/NCNTs, Pt/Ni/NCNTs displayed much wider detection ranges (0.5-40 mM and 40-110 mM) for nitrite sensing. The sensitivity is 276.92 µA mM-1 cm-2 and 224.39 µA mM-1 cm-2, respectively. The detection limit is 0.17 µM. The Pt/Ni/NCNTs sensors also showed good feasibility for nitrite sensing in real samples (milk and peach juice) analysis. The active Pt/Ni/NCNTs composites and facile fabrication technique may provide useful strategies to develop other sensitive nitrite sensors.

Maternity exclusion with a very high autosomal STRs kinship index.

This paper reports a maternity testing case to assess the biological relationship between a woman and the boy she was adopting. For all 46 tested autosomal STR loci, the adopting woman and the boy shared at least one allele at each locus, which supported that the woman could be the biological mother of the boy. The pairwise kinship indices (KIs) were calculated for various identity-by-descent distributions. Motherson was the most likely relationship with a very high KI (i.e., 6.91E+08) based on 35 independent autosomal STR loci, but KIs of other pairwise relationships (e.g., aunt-nephew, full sib, etc.) were also high. Further testing of X-STRs and mtDNA excluded the maternity relationship between woman and boy, in which 13 out of 20 X-STR loci were inconsistent and 18 nucleotide mismatches were observed at hypervariable regions I and II of the mtDNA. However, a more distant relationship (e.g., aunt-nephew) cannot be excluded. This case reinforces that possible false identifications can occur in kinship analysis cases yielding very high KIs.

Genetic polymorphisms of 12 X-STR for forensic purposes in Shanghai Han population from China.

X-chromosomal short tandem repeats (X-STR) loci are used for forensic practice in recent years in some complex kinship cases. The commercially available kit of Investigator Argus X-12 (Qiagen, Hilden, Germany) makes it possible to examine the markers of DXS10148-DXS10135-DXS8378, DXS7132-DXS10079-DXS10074, DXS10103-HPRTB-DXS10101 and DXS10146-DXS10134-DXS7423, which belong to four linkage groups of X-chromosome. In this study, a total of 309 unrelated individuals (200 males and 109 females) from Shanghai Han population were successfully analyzed with this kit. Hardy-Weinberg equilibrium tests demonstrated no significant deviation from expected values (P > 0.05) for all of the 12 X-STR loci in the Shanghai Han population. Linkage disequilibrium tests were performed for all pairs of loci by the Arlequin v3.1 software and only DXS10103-DXS10101 remained significant after adjustment for multiple testing (P < 0.05/66). The combined power of discrimination in males (CDP(M)) was 0.999999996 while in females (CDP(F)) was 0.999999999999995, and the combined mean exclusion chance in duo cases (CMEC(D)) was 0.999998 while in trio cases (CMEC(T)) was 0.999999986. The results suggest that the twelve X-STR loci may provide high polymorphic information for paternity testing and forensic identification in Chinese Han population from Shanghai.

Selection of 29 highly informative InDel markers for human identification and paternity analysis in Chinese Han population by the SNPlex genotyping system.

The interest of forensic researchers in single nucleotide polymorphism (SNP) has been attracted because of its potential advantages, such as low mutation rates, amenable to high-throughput automated platform and the improved application in the analysis of degraded samples. In this paper, 29 highly informative insertion/deletion (InDel, a special kind of SNP) markers were selected from the dbSNP ( http://www.ncbi.nlm.nih.gov/SNP/ ) according to the given criteria. 109 unrelated Chinese Han subjects were genotyped for the 29 InDels with SNPlex genotyping system. The allele frequency data revealed that the combined power of discrimination for the 29 InDel markers was 0.999999999990867 and the combined probability of paternity exclusion (PE) was 0.9930. Sensitivity studies were performed to evaluate the flexibility of the SNPlex genotyping system on the set of 29 InDels. Highly reproducible results could be obtained with 40-100 ng genomic DNA and the proportion of total allele drop-in was significantly increased when the amount of DNA added to PCR was lower than 35 ng. These results suggested that the set of 29 InDels was useful in paternity analysis or human identification in the future.