Targeting m6A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer.

OBJECTIVE: The role of N6-methyladenosine (m6A) in tumour immune microenvironment (TIME) remains understudied. Here, we elucidate function and mechanism of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in colorectal cancer (CRC) TIME. DESIGN: Clinical significance of YTHDF1 was assessed in tissue microarrays (N=408) and TCGA (N=526) cohorts. YTHDF1 function was determined in syngeneic tumours, intestine-specific Ythdf1 knockin mice, and humanised mice. Single-cell RNA-seq (scRNA-seq) was employed to profile TIME. Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) were used to identify YTHDF1 direct targets. Vesicle-like nanoparticles (VNPs)-encapsulated YTHDF1-siRNA was used for YTHDF1 silencing in vivo. RESULTS: YTHDF1 expression negatively correlated with interferon-γ gene signature in TCGA-CRC. Concordantly, YTHDF1 protein negatively correlated with CD8+ T-cell infiltration in independent tissue microarrays cohorts, implying its role in TIME. Genetic depletion of Ythdf1 augmented antitumour immunity in CT26 (MSS-CRC) and MC38 (MSI-H-CRC) syngeneic tumours, while Ythdf1 knockin promoted an immunosuppressive TIME facilitating CRC in azoxymethane-dextran sulphate-sodium or ApcMin/+ models. scRNA-seq identified reduction of myeloid-derived suppressor cells (MDSCs), concomitant with increased cytotoxic T cells in Ythdf1 knockout tumours. Integrated MeRIP-seq, RNA-seq and Ribo-seq revealed p65/Rela as a YTHDF1 target. YTHDF1 promoted p65 translation to upregulate CXCL1, which increased MDSC migration via CXCL1-CXCR2 axis. Increased MSDCs in turn antagonised functional CD8+ T cells in TIME. Importantly, targeting YTHDF1 by CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) or VNPs-siYTHDF1 boosted anti-PD1 efficacy in MSI-H CRC, and overcame anti-PD1 resistance in MSS CRC. CONCLUSION: YTHDF1 impairs antitumour immunity via an m6A-p65-CXCL1/CXCR2 axis to promote CRC and serves as a therapeutic target in immune checkpoint blockade therapy.

Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts antitumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis.

BACKGROUND & AIMS: RNA N6-methyladenosine (m6A) reader protein YTHDF1 has been implicated in cancer; however, its role in hepatocellular carcinoma (HCC), especially in non-alcoholic steatohepatitis-associated HCC (NASH-HCC), remains unknown. Here, we investigated the functional role of YTHDF1 in NASH-HCC and its interplay with the tumor immune microenvironment. METHODS: Hepatocyte-specific Ythdf1-overexpressing mice were subjected to a NASH-HCC-inducing diet. Tumor-infiltrating immune cells were profiled with single-cell RNA-sequencing, flow cytometry, and immunostaining. The molecular target of YTHDF1 was elucidated with RNA-sequencing, m6A-sequencing, YTHDF1 RNA immunoprecipitation-sequencing, proteomics, and ribosome-profiling. Ythdf1 in NASH-HCC models was targeted by lipid nanoparticle (LNP)-encapsulated small-interfering Ythdf1. RESULTS: YTHDF1 is overexpressed in tumor tissues compared to adjacent peri-tumor tissues from patients with NASH-HCC. Liver-specific Ythdf1 overexpression drives tumorigenesis in dietary models of spontaneous NASH-HCC. Single-cell RNA-sequencing and flow cytometry revealed that Ythdf1 induced accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed cytotoxic CD8+ T-cell function. Mechanistically, Ythdf1 expression in NASH-HCC cells induced the secretion of IL-6, which mediated MDSC recruitment and activation, leading to CD8+ T-cell dysfunction. EZH2 mRNA was identified as a key YTHDF1 target. YTHDF1 binds to m6A-modified EZH2 mRNA and promotes EZH2 translation. EZH2 in turn increased expression and secretion of IL-6. Ythdf1 knockout synergized with anti-PD-1 treatment to suppress tumor growth in NASH-HCC allografts. Furthermore, therapeutic targeting of Ythdf1 using LNP-encapsulated small-interfering RNA significantly increased the efficacy of anti-PD-1 blockade in NASH-HCC allografts. CONCLUSIONS: We identified that YTHDF1 promotes NASH-HCC tumorigenesis via EZH2-IL-6 signaling, which recruits and activates MDSCs to cause cytotoxic CD8+ T-cell dysfunction. YTHDF1 may be a novel therapeutic target to improve responses to anti-PD-1 immunotherapy in NASH-HCC. IMPACT AND IMPLICATIONS: YTHDF1, a N6-methyladenosine reader, is upregulated in patients with non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC); however, its role in modulating the tumor immune microenvironment in NASH-HCC remains unclear. Here, we show that Ythdf1 mediates immunosuppression in NASH-HCC and that targeting YTHDF1 in combination with immune checkpoint blockade elicits robust antitumor immune responses. Our findings suggest novel therapeutic targets for potentiating the efficacy of immune checkpoint blockade in NASH-HCC and provide the rationale for developing YTHDF1 inhibitors for the treatment of NASH-HCC.

METTL3 Inhibits Antitumor Immunity by Targeting m6A-BHLHE41-CXCL1/CXCR2 Axis to Promote Colorectal Cancer.

BACKGROUND & AIMS: N6-Methyladenosine (m6A) is the most prevalent RNA modification and recognized as an important epitranscriptomic mechanism in colorectal cancer (CRC). We aimed to exploit whether and how tumor-intrinsic m6A modification driven by methyltransferase like 3 (METTL3) can dictate the immune landscape of CRC. METHODS: Mettl3 knockout mice, CD34+ humanized mice, and different syngeneic mice models were used. Immune cell composition and cytokine level were analyzed by flow cytometry and Cytokine 23-Plex immunoassay, respectively. M6A sequencing and RNA sequencing were performed to identify downstream targets and pathways of METTL3. Human CRC specimens (n = 176) were used to evaluate correlation between METTL3 expression and myeloid-derived suppressor cell (MDSC) infiltration. RESULTS: We demonstrated that silencing of METTL3 in CRC cells reduced MDSC accumulation to sustain activation and proliferation of CD4+ and CD8+ T cells, and eventually suppressed CRC in ApcMin/+Mettl3+/- mice, CD34+ humanized mice, and syngeneic mice models. Mechanistically, METTL3 activated the m6A-BHLHE41-CXCL1 axis by analysis of m6A sequencing, RNA sequencing, and cytokine arrays. METTL3 promoted BHLHE41 expression in an m6A-dependent manner, which subsequently induced CXCL1 transcription to enhance MDSC migration in vitro. However, the effect was negligible on BHLHE41 depletion, CXCL1 protein or CXCR2 inhibitor SB265610 administration, inferring that METTL3 promotes MDSC migration via BHLHE41-CXCL1/CXCR2. Consistently, depletion of MDSCs by anti-Gr1 antibody or SB265610 blocked the tumor-promoting effect of METTL3 in vivo. Importantly, targeting METTL3 by METTL3-single guide RNA or specific inhibitor potentiated the effect of anti-programmed cell death protein 1 (anti-PD1) treatment. CONCLUSIONS: Our study identifies METTL3 as a potential therapeutic target for CRC immunotherapy whose inhibition reverses immune suppression through the m6A-BHLHE41-CXCL1 axis. METTL3 inhibition plus anti-PD1 treatment shows promising antitumor efficacy against CRC.

Effect of annualized surgeon volume on major surgical complications for abdominal and laparoscopic radical hysterectomy for cervical cancer in China, 2004-2016: a retrospective cohort study.

BACKGROUND: Previous studies have suggested that higher surgeon volume leads to improved perioperative outcomes for oncologic surgery; however, the effect of surgeon volumes on surgical outcomes might differ according to the surgical approach used. This paper attempts to evaluate the effect of surgeon volume on complications or cervical cancer in an abdominal radical hysterectomy (ARH) cohort and laparoscopic radical hysterectomy (LRH) cohort. METHODS: We conducted a population-based retrospective study using the Major Surgical Complications of Cervical Cancer in China (MSCCCC) database to analyse patients who underwent radical hysterectomy (RH) from 2004 to 2016 at 42 hospitals. We estimated the annualized surgeon volumes in the ARH cohort and in the LRH cohort separately. The effect of the surgeon volume of ARH or LRH on surgical complications was examined using multivariable logistic regression models. RESULTS: In total, 22,684 patients who underwent RH for cervical cancer were identified. In the abdominal surgery cohort, the mean surgeon case volume increased from 2004 to 2013 (3.5 to 8.7 cases) and then decreased from 2013 to 2016 (8.7 to 4.9 cases). The mean surgeon case volume number of surgeons performing LRH increased from 1 to 12.1 cases between 2004 and 2016 (P < 0.01). In the abdominal surgery cohort, patients treated by intermediate-volume surgeons were more likely to experience postoperative complications (OR = 1.55, 95% CI = 1.11-2.15) than those treated by high-volume surgeons. In the laparoscopic surgery cohort, surgeon volume did not appear to influence the incidence of intraoperative or postoperative complications (P = 0.46; P = 0.13). CONCLUSIONS: The performance of ARH by intermediate-volume surgeons is associated with an increased risk of postoperative complications. However, surgeon volume may have no effect on intraoperative or postoperative complications after LRH.

Robust and Radiation-Resistant Hofmann-Type Metal-Organic Frameworks for Record Xenon/Krypton Separation.

The discovery of high-performance adsorbents for highly efficient separation of xenon from krypton is an important but challenging task in the chemical industry due to their similar size and inert spherical nature. Herein, we report two robust and radiation-resistant Hofmann-type MOFs, Co(pyz)[Ni(CN)4] and Co(pyz)[Pd(CN)4] (termed as ZJU-74a-Ni and ZJU-74a-Pd), featuring oppositely adjacent open metal sites and perfect pore sizes (4.1 and 3.8 Å) comparable to the kinetic diameter of xenon (4.047 Å), affording the benchmark binding affinity for polarizable Xe gas. These materials thus exhibit both record-high Xe uptake capacities (89.3 and 98.4 cm3 cm-3 at 296 K and 0.2 bar) and Xe/Kr selectivities (74.1 and 103.4) at ambient conditions, all of which are the highest among all the state-of-the-art materials reported so far. The locations of Xe molecules within ZJU-74a-Ni have been visualized by single-crystal X-ray diffraction studies, in which two oppositely adjacent metal centers combined with the right aperture size can construct a unique sandwich-like binding site to offer unprecedented and ultrastrong Ni2+-Xe-Ni2+ interactions with xenon, thus leading to the record Xe capture capacity and selectivity. The excellent separation capacity of ZJU-74a-Pd was verified by breakthrough experiments for Xe/Kr gas mixtures, providing both unprecedentedly high xenon uptake capacity (4.63 mmol cm-3) and krypton productivity (214 cm3 g-1).

Lactobacillus derived from breast milk facilitates intestinal development in IUGR rats.

AIM: The intestinal microbiota contributes to infant's intestine homeostasis. This study aimed to analyse how probiotics derived from breast milk promote infant intestinal development in rat pups. METHODS AND RESULTS: The effect of potential probiotics derived from breast milk on development of intrauterine growth retardation (IUGR) newborn rats' intestine was investigated. Limosilactobacillus oris ML-329 and Lacticaseibacillus paracasei ML-446 exhibited good hydrophobicity percentages (p < 0.05). ML-446 showed a significant effect on intestinal length and weight (p < 0.05). Meanwhile, the villus height of the IUGR newborn rats fed with ML-329 was significantly higher compared with those fed with Lacticaseibacillus rhamnosus GG (p < 0.05). Moreover, ML-329 and ML-446 both significantly stimulated the proliferation and differentiation of intestinal epithelial cells by increasing the number of ki67-positive cells, goblet cells, and lysozyme-positive Paneth cells (p < 0.05) through Wnt and Notch pathway. CONCLUSIONS: The proliferation and differentiation stimulating effects of ML-329 and ML-446 on IECs in the jejunum, ileum, and colon were mediated by activating the Wnt pathway with increased expression of wnt, lrp5, and ß-catenin genes and accumulation of ß-catenin, and by downregulating the Notch signalling pathway with decreased expression of the activated notch protein. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus could facilitate IUGR rat pups' intestinal development and enhance the proliferation of Paneth cells and goblet cells. These findings provide further insights into promotion of the intestinal development by breast milk-derived beneficial microbes in early life of the IUGR newborn rats.

Critical cultural competence of clinical nurses in China: A cross-sectional survey.

AIM: To determine the level of critical cultural competence (CCC) among Chinese clinical nurses and explore its influencing factors. BACKGROUND: Previous research has only focused on the theoretical model of CCC and the development of assessment tools; however, no large-scale study has been conducted on the level of clinical nurses' CCC and its influencing factors. METHOD: Clinical nurses in 14 Level A tertiary hospitals (n = 3858) were surveyed using Almutairi's critical cultural competence scale (CCCS). Descriptive, univariate and multivariate analyses were performed. RESULTS: The mean score of CCC was 4.44 (SD = 0.33). Critical empowerment (M = 4.85, SD = 0.58) and critical awareness (M = 3.57, SD = 0.99) had the highest and lowest scores, respectively. Female nurses, nurses in the nursing department and nurses with higher positions had higher CCC. CONCLUSION: The CCC of clinical nurses can be strengthened through targeted training, especially considering the fact that male and low-ranking nurses who had the lower level of CCC work in different departments. IMPLICATIONS FOR NURSING MANAGEMENT: Hospital administrators should pay attention to the importance of culture and cultural differences among different countries or ethnic groups. Creating an equal and fair nursing environment and encouraging nurses to provide critical cultural nursing is important.

Evaluation of reliability and validity regarding the Chinese version of Critical Cultural Competence Scale for clinical nurses. / 临床护士评判性文化能力量表的汉化及信效度评价.

OBJECTIVES: Patients from different social environments and cultural backgrounds have different nursing needs. If nurses ignore the cultural differences of patients, it is easy to lead to the strained nurse-patient relationship, affect the nursing effect and cause harm to patients. Critical cultural competence (CCC) can help nurses to meet the nursing needs of patients from different cultural backgrounds, which is beneficial to building a harmonious nurse-patient relationship and improving the quality of nursing. Almutairi, et al designed the Critical Cultural Competence Scale (CCCS) which can be used to evaluate accurately nurses' CCC. No studies have reported the development of a critical cultural competence measurement tool for nurses or the introduction of foreign scales in China. This study aims to conduct Chinese and cross-cultural debugging and test the reliability of the English version of the CCCS in order to form CCCS suitable for Chinese cultural background and provide an effective evaluation tool for investigating the current situation of clinical nurses' CCC. METHODS: This study used Brislin's back-translation model to translate and back-translation the English version of CCCS. The Chinese version of CCCS was then created through cross-cultural debugging by expert consultation and a pre-survey with a sample size of 30 clinical nurses. From August to October 2019, 580 clinical nurses were surveyed using a whole group sampling method. The participants were randomly divided into 2 groups with a 7꞉3 ratio. One group (n=406) was used for exploratory factor analysis and reliability analysis, while the other group (n=174) was used for confirmatory factor analysis. Six experts used the scale-level content validity index (S-CVI) and the item-level content validity index (I-CVI) to assess content validity. In the exploratory factor analysis, items were screened using the critical ratio method, and were tested using the KMO (Kalser-Meyer-Olkin) index, Bartlett's sphericity test, and principal component analysis. In the confirmatory factor analysis, average variance extracted (AVE), goodness of fit index (GFI), adjusted goodness of fit index (AGFI), and root mean square error of approximation (RMSEA) were used to assess the degree of fit of the constructed model. For the total scale and the 4 subscales, the Cronbach's α coefficient, split-half reliability, and retest reliability were used to assess the scale's reliability. RESULTS: The S-CVI was 0.930, while the I-CVI ranged from 0.833 to 0.944. For all items, the critical ratio exceeded 3, and the difference between the high and low subgroups was statistically significant (P<0.05). Exploratory factor analysis revealed critical knowledge subscale had a KMO value of 0.676, with the total scale and other 3 subscales all having a KMO value >0.8 and a chi-square value of 814.32 to 12 442.45 for the Bartlett's spherical test, with degree of freedom ranging from 21 to 136 (P<0.001), indicating that all items were suitable for factor analysis. The principal component analysis showed that 17, 12, 7, and 7 items were extracted from the 4 subscales, with 4, 3, 2, and 2 components whose eigenvalues were more than 1, and the cumulative variance contribution was 66.0%, 54.3%, 56.6%, and 70.2%, respectively. The confirmatory factor analysis showed that the AVE of the 4 subscales were 0.637, 0.499, 0.560, and 0.565, GFI was 0.904, AGFI was 0.863, and RMSEA was 0.076. The Cronbach's α coefficient for the total scale and subscales ranged from 0.811 to 0.878, the split-half reliability ranged from 0.707 to 0.842, and the retest reliability was 0.827. CONCLUSIONS: The Chinese version of the CCCS has good reliability and validity, and it can be used as a valid assessment tool for clinical nurses' critical cultural competence in China.

Engineering Supramolecular Binding Sites in a Chemically Stable Metal-Organic Framework for Simultaneous High C2 H2 Storage and Separation.

Developing porous materials to overcome the trade-off between adsorption capacity and selectivity for C2 H2 /CO2 separation remains a challenge. Herein, we report a stable HKUST-1-like MOF (ZJU-50a), featuring large cages decorated with high density of supramolecular binding sites to achieve both high C2 H2 storage and selectivity. ZJU-50a exhibits one of the highest C2 H2 storage capacity (192 cm3 g-1 ) and concurrently high C2 H2 /CO2 selectivity (12) at 298 K and 1 bar. Single-crystal X-ray diffraction studies on gas-loaded ZJU-50a crystal unveil that the incorporated supramolecular binding sites can selectively take up C2 H2 molecule but not CO2 to result in both high C2 H2 storage and selectivity. Breakthrough experiments validated its separation performance for C2 H2 /CO2 mixtures, providing a high C2 H2 recovery capacity of 84.2 L kg-1 with 99.5 % purity. This study suggests a novel strategy of engineering supramolecular binding sites into MOFs to overcome the trade-off for this separation.

Zeolite NPO-Type Azolate Frameworks.

Three-membered rings (3-rings) are an important structural motif in zeolite chemistry, but their formation remains serendipitous in reticular chemistry when designing zeolitic imidazolate frameworks (ZIFs). Herein, we report a design principle for constructing four new ZIFs, termed ZIF-1001 to -1004, from tetrahedral ZnII centers (T), benzotriazolate (bTZ), and different functionalized benzimidazolates (RbIM) that adopt a new zeolite NPO-type topology built from 3-rings. Two factors were critical for this discovery: i) incorporating the bTZ linker within the structures formed 3-rings due to a ∠(T-bTZ-T) angle of 120-130° reminiscent of the ∠(Ge-O-Ge) angle (130°) observed in germanate zeolite-type structures having 3-rings; and ii) RbIM guided the coordination chemistry of bTZ to bind preferentially in an imidazolate-type mode. This series' ability to selectively capture CO2 from high-humidity flue gas and trap ethane from tail gas during shale gas extraction was demonstrated.

Lactobacillus gallinarum modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis.

OBJECTIVE: Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis. DESIGN: The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry. RESULTS: L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo. CONCLUSION: L. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.

Breast milk contains probiotics with anti-infantile diarrhoea effects that may protect infants as they change to solid foods.

Infants often experience complementary food-induced diarrhoea (CFID), which occurs when infants switch from breast milk to solid foods. The relative abundances of Prevotella and Rothia were higher in stools of infants with CFID, while the relative abundances of Enterococcus and Escherichia were higher in healthy infants. The abundance of Lactobacillus spp. normally found in breast milk fed to infants with CFID was significantly reduced, and Enterococcus spp. were less abundant when diarrhoea occurred. Furthermore, Lactobacillus and Enterococcus were present as shared bacteria in both mother and infant, and they were considered potential anti-CFID probiotics as their relative abundances in breast milk were negatively correlated to infant CFID. Kyoto encyclopedia of genes and genomes (KEGG) functional analysis showed that the function of amino acid metabolism differed between infants with CFID and healthy infants. Therefore, CFID might be related to the decomposition of proteins in food supplements. The screening revealed seven hydrolytic casein and five hydrolytic casein and rice protein isolates from 320 suspected Lactobacillus and Enterococcus isolates. The animal experiments demonstrated that a mixture of five isolates effectively hydrolysed the casein and rice protein and prevented diarrhoea in young rats. Thus, the occurrence of CFID was found to be closely related to the intestinal and breast milk microbiota, and bacteria that could assist in the digestion of cereal proteins were involved in CFID.

The mammalian decidual cell evolved from a cellular stress response.

Among animal species, cell types vary greatly in terms of number and kind. The number of cell types found within an organism differs considerably between species, and cell type diversity is a significant contributor to differences in organismal structure and function. These observations suggest that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms that result in the evolution of novel cell types, however, are poorly understood. Here, we show that a novel cell type of eutherians mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESFs, the majority of decidual core regulatory genes respond to decidualizing signals but do not regulate decidual effector genes. Rather, in opossum ESFs, decidual transcription factors function in apoptotic and oxidative stress response. We propose that rewiring of cellular stress responses was an important mechanism for the evolution of the eutherian decidual cell type.

Built environment and the metropolitan pandemic: Analysis of the COVID-19 spread in Hong Kong.

The COVID-19 reported initially in December 2019 led to thousands and millions of people infections, deaths at a rapid scale, and a global scale. Metropolitans suffered serious pandemic problems as the built environments of metropolitans contain a large number of people in a relatively small area and allow frequent contacts to let virus spread through people's contacting with each other. The spread inside a metropolitan is heterogeneous, and we propose that the spatial variation of built environments has a measurable association with the spread of COVID-19. This paper is the pioneering work to investigate the missing link between the built environment and the spread of the COVID-19. In particular, we intend to examine two research questions: (1) What are the association of the built environment with the risk of being infected by the COVID-19? (2) What are the association of the built environment with the duration of suffering from COVID-19? Using the Hong Kong census data, confirmed cases of COVID-19 between January to August 2020 and large size of built environment sample data from the Hong Kong government, our analysis are carried out. The data is divided into two phases before (Phase 1) and during the social distancing measure was relaxed (Phase 2). Through survival analysis, ordinary least squares analysis, and count data analysis, we find that (1) In Phase 1, clinics and restaurants are more likely to influence the prevalence of COVID-19. In Phase 2, public transportation (i.e. MTR), public market, and the clinics influence the prevalence of COVID-19. (2) In Phase 1, the areas of tertiary planning units (i.e., TPU) with more restaurants are found to be positively associated with the period of the prevalence of COVID-19. In Phase 2, restaurants and public markets induce long time occurrence of the COVID-19. (3) In Phase 1, restaurant and public markets are the two built environments that influence the number of COVID-19 confirmed cases. In Phase 2, the number of restaurants is positively related to the number of COVID-19 reported cases. It is suggested that governments should not be too optimistic to relax the necessary measures. In other words, the social distancing measure should remain in force until the signals of the COVID-19 dies out.

MTHFR-C677T Gene Polymorphism and Susceptibility to Acute Lymphoblastic Leukemia in Children: A Meta-Analysis.

BACKGROUND: The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) and childhood acute lymphoblastic leukemia (ALL) is inconsistent. OBJECTIVE: To explore the relationship between MTHFR-C677T polymorphism and susceptibility to childhood ALL. METHODS: PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP, and other databases were searched from the establishment of the database to November 2019, and all the case-control studies that met the inclusion criteria were collected. Stata 15.0 was used for meta-analysis, with calculation of the odds ratio (OR) of the relationship between MTHFR-C677T polymorphism and childhood ALL susceptibility. Ethnicity was analyzed by subgroup analysis. RESULTS: A total of 26 studies were included in this meta-analysis, including 4,682 children with ALL and 7144 controls. The results showed that there was no significant difference in the comparison of population of allele model, dominant gene model, recessive gene model, homozygous gene model, heterozygous gene model, and the comparison of Caucasian children. The results of the Asian child analysis suggested that the combined OR of the dominant gene model (CC + CT versus TT), homozygous model (CC versus TT) and heterozygous model (CT versus TT) was 1.32 (95% confidence interval [CI]: 1.03-1.70), 1.37 (95% CI: 1.02-1.84), and 1.27 (95% CI: 1.01-1.59), respectively, with statistically significant differences. However, there was no significant difference between the allele model and recessive gene model among Asian children. CONCLUSION: The MTHFR C677T polymorphism is related to ALL in children, especially in Asian children. CC + CT, CC, and CT genotypes can increase the risk of ALL, but no association has been found in Caucasian children.

Effect of laparoscopic versus abdominal radical hysterectomy on major surgical complications in women with stage IA-IIB cervical cancer in China, 2004-2015.

OBJECTIVES: To report the trends in surgical approaches and compare the major surgical complication rates of laparoscopic and abdominal radical hysterectomy for cervical cancer. METHODS: From the major surgical complications of cervical cancer in China (MSCCCC) database, we obtained the demographic, clinical, treatment hospital and complication data of patients with cervical cancer who underwent radical hysterectomy from 2004 to 2015 at 37 hospitals. The patients were assigned to the laparoscopic and abdominal surgery groups. The differences in the complication rates were analyzed using univariate and multivariable logistic regression models. RESULTS: We identified a total of 18447 patients; 5491 (29.8%) underwent laparoscopic surgery and 12956 (70.2%) underwent abdominal surgery. The proportion of laparoscopic surgery rose from 0.35% in 2004 to 49.31% in 2015. In the multivariate analysis, the laparoscopic group had increased odds of intraoperative and postoperative complications (OR = 3.88, 95% CI = 2.47-6.11; OR = 1.42, 95% CI = 1.11-1.82). A more detailed analysis showed that laparoscopic surgery was associated with increased rates of intraoperative ureteral injury (OR = 3.83, 95% CI = 2.11-6.95), bowel injury (OR = 14.83, 95% CI = 1.32-167.25), vascular injury (OR = 3.37, 95% CI = 1.18-9.62), postoperative vesicovaginal fistula (OR = 4.16, 95% CI = 2.08-8.32), ureterovaginal fistula (OR = 4.16, 95% CI = 2.08-8.32), rectovaginal fistula (OR = 8.04, 95% CI = 1.63-39.53), and chylous leakage (OR = 10.65, 95% CI = 1.18-95.97), while abdominal surgery was more likely to cause bowel obstruction (OR = 0.55, 95% CI = 0.35-0.87). The two groups had similar rates of bladder injury, obturator nerve injury, pelvic hematoma, rectovaginal fistula and venous thromboembolism (P > 0.05). CONCLUSION: Laparoscopic surgery was associated with more major surgical complications, especially intraoperative ureteral injury and postoperative fistula, than abdominal surgery among women with cervical cancer.

Risk factors and long-term impact of urologic complications during radical hysterectomy for cervical cancer in China, 2004-2016.

OBJECTIVE: The primary objective was to describe the incidence and risk factors of urologic complications during radical hysterectomy for cervical cancer. The secondary objective was to investigate the impact of urologic complications on long-term survival. METHODS: Patients who underwent radical hysterectomy for cervical cancer from 2004 to 2016 were identified in the MSCCCC (Major Surgical Complications of Cervical Cancer in China) database. Data on demographic characteristics, clinical characteristics, hospital characteristics and urologic complications were collected. Multivariable logistic regression was used to assess the risk factors of urologic complications and Cox proportional hazards models were performed to identify prognostic factors. RESULTS: A total of 21,026 patients undergoing radical hysterectomy for cervical cancer were identified. The incidence of any urologic complications was 1.54%: 83 (0.39%) ureteral injuries, 17 (0.08%) bladder injuries, 1 (0.005%) ureteral injury combined with bladder injury, and 223 (1.05%) genitourinary fistulas. In a multivariable analysis, surgery at a women and children's hospital (OR = 2.26, 95% CI 1.47-3.48), surgery at a facility in a first-tier city (OR = 2.08, 95% CI 1.24-3.48), and laparoscopic surgery (OR = 4.68, 95% CI 3.44-6.36) were associated with a higher risk of urologic complications. Cox proportional hazards models revealed that the occurrence of urologic complications was a significant predictor of 2-year overall survival (OR = 1.78, 95% CI = 1.09-2.92), but was not a predictor of 5-year overall survival (OR = 1.27, 95% CI = 0.83-1.94). CONCLUSION: The incidence of urologic complications during radical hysterectomy is low. The risk of urologic complications may be higher for patients who are treated at a women and children's hospital, are treated in first-tier city hospitals, and receive laparoscopic surgery. Urologic complications have an impact on short-term survival, but not on long-term survival.

Modulator-Induced Zr-MOFs Diversification and Investigation of Their Properties in Gas Sorption and Fe3+ Ion Sensing.

In this paper, we synthesized three Zr-MOFs (Zr-SXU-1, Zr-SXU-2, and Zr-SXU-3) composed of identical ligands and metal clusters by using tetratopic carboxylic ligand PBPTTBA as the ligand and benzoic acids as modulators. These three Zr-MOFs showed different structures and topologies, and the connectivity of the Zr clusters varied from 8 in Zr-SXU-3, to 10 in Zr-SXU-1, and finally to 12 in Zr-SXU-2 due to the modulators used. Among them, Zr-SXU-1 represents an unusual 6-node network and [6(10)(11)7] transitivity. Besides, Zr-SXU-2 can only be obtained by using ditopic carboxylic acid as a second modulator when using benzoic acid as the main modulator, which is not reported in other Zr-MOFs synthesis. The adsorption and luminescence tests demonstrated their potential as gas reservoirs, separators, and sensors and also showed the importance of structure topologies to the applications.

A modified microsurgical interfacet release and direct distraction technique for management of congenital atlantoaxial dislocation: technical note.

Various techniques have been used for management of congenital atlantoaxial dislocation. Recently, the reduction of atlantoaxial dislocation through a single posterior approach has attracted more and more attention. Here, we present a modified technique including direct interfacet release and distraction between C1 and C2 by a specially designed distractor, posterior internal fixation and bone graft fusion. The illustrated technique was performed in 15 consecutive patients, and the outcomes were recorded and analyzed. Follow-up ranged from 12 to 26 months. Clinical symptoms improved in 14 patients (93.3%) and were stable in 1 patient (6.7%). Radiologically, 60-100% reduction was achieved in 13 patients (86.6%). Bone fusion was obtained in all patients at 12 months after the operation. The two-tailed Wilcoxon signed-rank test was used to analyze the preoperative and postoperative Japanese Orthopedic Association scores (JOA), atlas-dens interval (ADI), and cervicomedullary angle (CMA) (P < 0.001). Our results suggested that this direct interfacet release and distraction technique with a specially designed C1-2 distractor can provide a definite effective C1-2 facet distraction and odontoid process restoration through a single posterior approach.

The effects of temperature and dissolved oxygen on the growth, survival and oxidative capacity of newly hatched hybrid yellow catfish larvae (Tachysurus fulvidraco♀ × Pseudobagrus vachellii♂).

Demand for yellow catfish fry, an economically important farmed fish in China, has increased dramatically. Newly hatched larvae are highly sensitive to changes in environmental conditions, with water temperature (T) and dissolved oxygen (DO) being two important factors that affect their early development. We investigate optimal T (between 19.0 and 33.0 °C) and DO (between 2.0 and 12.0 mg L-1) concentrations on growth and antioxidant enzyme activity of newly hatched hybrid yellow catfish larvae (Tachysurus fulvidraco × Pseudobagrus vachellii) using a central composite design. We use a response surface method to optimize the response variables for survival (S) and growth, and the reduction of oxidative stress, over a 50-day experimental duration. T has a significant effect on specific growth rate (SGR), hepatic malondialdehyde (MDA) content, and superoxide dismutase (SOD) and catalase (CAT) activities (P < 0.05). DO concentration has a significant effect on SGR, S, hepatic MDA content, and SOD and CAT activities (P < 0.05). T and DO also have significant second order effects on SGR, S, SOD, and CAT activities (P < 0.05). Increased DO at low T stimulates SOD and CAT activities and alleviates oxidative damage. Adjusted R2 values for SGR, S, CAT, SOD, and MDA models are 0.734, 0.937, 0.916, 0.894 and 0.826, respectively. A combination of 26.8 °C and 7.3 mg L-1 represents optimal rearing conditions, in that larval growth and antioxidant ability is improved. Results show that T and DO during larviculture of yellow catfish have important implications for aquaculture.