Cu-Catalyzed Carbocyclization for General Synthesis of N-Containing Heterocyclics Enabled by BrCF2COOEt as a C1 Source.

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

High-risk human papillomavirus genotype distribution among women living with and at risk for HIV in Africa.

OBJECTIVE: Cervical cancer is a common preventable cancer among African women living with HIV (WLWH). Molecular diagnostics for high-risk human papillomavirus (HR-HPV) genotypes are standard components of cervical cancer screening in resource-rich countries but not in resource-limited settings. We evaluated HR-HPV genotypes among women with and without HIV in four African countries to inform cervical cancer preventive strategies. METHODS: The African Cohort Study (AFRICOS) enrolled participants with and without HIV at 12 clinics in Tanzania, Kenya, Uganda, and Nigeria. Cervical cytobrush specimens from women were genotyped for 14 HR-HPV types using the multiplex Seegene Anyplex real-time PCR assay. Robust Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with HR-HPV in WLWH. RESULTS: From January 2015 to March 2020, 868 WLWH and 134 women living without HIV (WLWoH) were tested for HR-HPV with prevalence of 50.9 and 38.1%, respectively ( P  = 0.007). Among WLWH, 844 (97.4%) were antiretroviral therapy (ART)-experienced and 772 (89.7%) virally suppressed 1000 copies/ml or less. The most frequent HR-HPV types among WLWH were HPV-16 (13.5%), HPV-52 (9.5%), and HPV-35 (9.3%). HR-HPV infection was more common among Tanzanian WLWH (adjusted RR: 1.23, 95% CI 1.05-1.44, P  = 0.012). Also, WLWH with CD4 + T cells of less than 200 cell/µl had 1.51-fold increased risk of having HR-HPV (95% CI 1.23-1.86, P  < 0.001). CONCLUSION: HR-HPV was common in WLWH in four African countries, particularly among women with low CD4 + cell count. Scale up of HPV vaccines and development of vaccines with broader activity against less common HR-HPV types may improve cervical cancer prevention in Africa.

Exogenous melatonin improved photosynthetic efficiency of photosystem II by reversible phosphorylation of thylakoid proteins in wheat under osmotic stress.

It has been well demonstrated that melatonin plays an important protective role in photosynthesis of plants under various environmental stresses, while the detailed mechanisms by which melatonin protects photosystem II (PSII) under environmental stress are still unclear. In the study, the effects of melatonin on photosynthetic efficiency, energy dissipation, PSII protein composition, and reversible phosphorylation of thylakoid proteins were investigated in wheat plants under osmotic stress. The results showed that osmotic stress significantly reduced pigment content, photochemical efficiency of PSII, oxygen-evolving activity, and dissipation of excess excitation energy, while 25 µM melatonin applications greatly alleviated their decline under osmotic stress. Western blot data of PSII proteins revealed that melatonin upregulated the levels of D1, Lhcb5, Lhcb6, PsbQ, and PsbS proteins in wheat exposed to osmotic stress. In addition, thylakoid membrane proteins were strongly phosphorylated in wheat under osmotic stress with or without melatonin. Furthermore, the results from PSII protein dephosphorylation showed that exogenous melatonin promoted the dephosphorylation of LCHII, CP43, and D1 under osmotic stress. Therefore, our findings suggest that melatonin can provide an effective protection for the photosynthetic apparatus by the regulation of PSII proteins and the reversible phosphorylation of thylakoid proteins under drought stress.

Recent Progress of Cellulose-Based Hydrogel Photocatalysts and Their Applications.

With the development of science and technology, photocatalytic technology is of great interest. Nanosized photocatalysts are easy to agglomerate in an aqueous solution, which is unfavorable for recycling. Therefore, hydrogel-based photocatalytic composites were born. Compared with other photocatalytic carriers, hydrogels have a three-dimensional network structure, high water absorption, and a controllable shape. Meanwhile, the high permeability of these composites is an effective way to promote photocatalysis technology by inhibiting nanoparticle photo corrosion, while significantly ensuring the catalytic activity of the photocatalysts. With the growing energy crisis and limited reserves of traditional energy sources such as oil, the attention of researchers was drawn to natural polymers. Like almost all abundant natural polymer compounds in the world, cellulose has the advantages of non-toxicity, degradability, and biocompatibility. It is used as a class of reproducible crude material for the preparation of hydrogel photocatalytic composites. The network structure and high hydroxyl active sites of cellulose-based hydrogels improve the adsorption performance of catalysts and avoid nanoparticle collisions, indirectly enhancing their photocatalytic performance. In this paper, we sum up the current research progress of cellulose-based hydrogels. After briefly discussing the properties and preparation methods of cellulose and its descendant hydrogels, we explore the effects of hydrogels on photocatalytic properties. Next, the cellulose-based hydrogel photocatalytic composites are classified according to the type of catalyst, and the research progress in different fields is reviewed. Finally, the challenges they will face are summarized, and the development trends are prospected.

A Reduction Active Theranostic Nanoparticle for Enhanced Near-Infrared Imaging and Phototherapy by Reducing Glutathione Level in Cancer Cells.

Facile preparation of a tumoral-stimuli-activated theranostic nanoparticle with simple constituents remains a challenge for tumor theranostic nanosystems. Herein we design a simple reductionresponsive turn-on theranostic nanoparticle for achieving fluorescent imaging and phototherapy combination. The theranostic nanoparticle is prepared by a simple one-step dialysis method of reduction active amphiphilic hyperbranched poly(ß-amidoamines) and a near-infrared (NIR) dye indocyanine green (ICG). The fluorescence of ICG is quenched by the aggregation-caused quenching (ACQ) effect. The fluorescent intensity of free ICG at 816 nm was ∼40 times as high as that of particulate ICG. After reductive nanoparticles incubated with dithiothreitol (DTT), the size of the nanoparticles increased from 160 nm to 610 nm by Dynamic light scattering (DLS). As nanoparticles were internalized by cancer cells, the disulfide bonds would be cleaved by intracellular reduction agents like glutathione (GSH), leading to the release of entrapped ICG. The released ICG regained its fluorescence for self-monitoring the release and therapeutic effect of ICG by fluorescence spectra and the quantitative evaluation of NIR fluorescence intensity. Remarkably, nanoparticles can also reinforce antitumor efficacy through photodynamic therapy and GSH depletion property. This study provides new insights into designing turn-on theranostic systems.

Nursing of Gastrointestinal Peristalsis Function Recovery after Abdominal Mirror Surgery for Rectal Cancer Patients Based on Intelligent Electronic Medicine.

In recent years, with the rapid development of colorectal surgery technology and laparoscopic instruments, laparoscopic radical resection of colorectal cancer has been widely used. Although laparoscopic surgery has the characteristics of small trauma, less blood loss, less hospitalization days, and low incidence of adverse reactions such as incision infection, it is still inevitable to have different degrees of gastrointestinal dysfunction after surgery. This paper mainly studies the recovery nursing of gastrointestinal peristalsis after abdominal mirror in rectal cancer patients based on intelligent electronic medicine. In this paper, an intelligent medical monitoring system is designed for the posterior care of rectal cancer patients with abdominal mirror image, which can realize the collection and transmission of wireless sign parameters of postoperative rectal cancer patients and improve the efficiency of postoperative monitoring in medical work. All parameter data are sent to the Lora base station in real time via Lora wireless communication, which is then uploaded to the medical monitoring platform. The experimental results showed that the first postoperative exhaust time of the treatment group using the intelligent medical monitoring system was significantly shortened, and the difference was statistically significant (P < 0.05). The first defecation time was shortened, and the difference was statistically significant (P < 0.05). The recovery time of total fluid diet was shortened, and the difference was statistically significant (P < 0.05). The above results indicate that the intelligent medical monitoring device designed in this paper has positive significance for improving the work efficiency of the hospital, the clinical experience of patients after abdominal mirror surgery for rectal cancer, and the real-time monitoring of signs of patients in intensive care.

Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent response for novel coronavirus disease 2019 (COVID-19). This study aimed to explore the roles of ACE2, apelin and sodium-glucose cotransporter 2 (SGLT2) in SARS-CoV-2-mediated cardiorenal damage. METHODS AND RESULTS: The published RNA-sequencing datasets of cardiomyocytes infected with SARS-CoV-2 and COVID-19 patients were used. String, UMAP plots and single cell RNA sequencing data were analyzed to show the close relationship and distinct cardiorenal distribution patterns of ACE2, apelin and SGLT2. Intriguingly, there were decreases in ACE2 and apelin expression as well as marked increases in SGLT2 and endothelin-1 levels in SARS-CoV-2-infected cardiomyocytes, animal models with diabetes, acute kidney injury, heart failure and COVID-19 patients. These changes were linked with downregulated levels of interleukin (IL)-10, superoxide dismutase 2 and catalase as well as upregulated expression of profibrotic genes and pro-inflammatory cytokines/chemokines. Genetic ACE2 deletion resulted in upregulation of pro-inflammatory cytokines containing IL-1ß, IL-6, IL-17 and tumor necrosis factor α. More importantly, dapagliflozin strikingly alleviated cardiorenal fibrosis in diabetic db/db mice by suppressing SGLT2 levels and potentiating the apelin-ACE2 signaling. CONCLUSION: Downregulation of apelin and ACE2 and upregulation of SGLT2, endothelin-1 and pro-inflammatory cytokines contribute to SARS-CoV-2-mediated cardiorenal injury, indicating that the apelin-ACE2 signaling and SGLT2 inhibitors are potential therapeutic targets for COVID-19 patients.

The proximity of the G-quadruplex to hemin impacts the intrinsic DNAzyme activity in mitochondria.

The DNAzyme activity of G-quadruplex/hemin in mitochondria has not been characterized. Herein, we report an unexpected difference in the DNAzyme activity between in vitro assays and in mitochondria. Molecular dynamic simulations illustrate how the interaction of the G-quadruplex with hemin may modulate the DNAzyme activity. These results might facilitate a better understanding of the catalytic mechanism of the DNAzyme and help the rational design of stable and active DNAzymes suitable for intracellular catalysis.

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging.

Theranostic nanosystems are emerging as a promising approach for controlled drug delivery, diagnosis and multimodal therapeutics. Herein, a multifunctional theranostic nanoplatform is reported for photothermal-chemo combination therapy functioned with magnetic and thermal imaging. Hyaluronic acid (HA) coated Fe3O4@polydopamine nanoparticles equipped with redox-sensitive disulfide linkers have been subsequently deposited with an anticancer drug, doxorubicin (DOX) (termed as FPCH-DOX NPs). These nanocomposites possess an average diameter of 120 nm, a saturation magnetization of 28.5 emu g-1, DOX loading capacity of 7.13% and a transverse relaxation rate of 171.76 mM-1 s-1. The drug release could be triggered by pH, glutathione (GSH) concentration and light irradiation. Prussian blue staining and confocal microscopy demonstrate that these nanoplatforms have improved biocompatibility and cellular uptake in CD44-positive HeLa cell lines rather than in CD44-negative NIH 3T3 normal cell lines. In vitro evaluations demonstrate that the combination therapy of FPCH-DOX NPs lowers the cell viability to 16.2%, less than that of individual chemotherapy (55.3%) or PTT (52.1%). In vivo MRI indicates that the tumor accumulation of FPCH-DOX NPs provides enhanced MRI contrast, and in vivo thermal imaging verified their localized photothermal conversion effect in tumor tissues. Importantly, FPCH-DOX NPs present remarkable anti-tumor efficacy by photothermal-chemo combination therapy. H&E and Ki67 staining tests show obvious necrosis and weak cell proliferation at the region of the tumor. Thus, FPCH-DOX NPs are promising multifunctional nanoplatforms for highly effective cancer theranostics.

A rapid, accurate and sensitive method for determination of monosaccharides in different varieties of Osmanthus fragrans Lour by pre-column derivatization with HPLC-MS/MS.

A specific HPLC-MS/MS (High-Performance Liquid Chromatography with tandem Mass Spectrometry) method was developed and validated for simultaneous determination of several monosaccharides in three kinds Osmanthus fragrans Lour. After extraction, separation, protein removal, pigment removal and hydrolysis, monosaccharides was finally obtained from Osmanthus fragrans Lour. Positive ion mode detection and Multiple Reaction Monitoring (MRM) mode were used for quantitative analysis by PMP pre-column derivatization and Electrospray Ionization (ESI). Analysis and content determination of 6 monosaccharide components in 3 kinds of Osmanthus fragrans Lour. The HPLC separation was achieved on a Shim-pack VP-ODS6022748 (150 L × 2.0) with gradient elution at a flow rate of 0.2 ml/min in a run time of 40 min, and the mobile phase was acetonitrile-5 mmol/L ammonium acetate. PMP derivatization in HPLC-MS/MS can accurately measure Osmanthus fragrans Lour. mannose (Man), ribose (Rib), rhamnose (Rha), galacturonic acid (Gal UA), glucose (Glu), galactose (Gal), xylose (Xyl), fucose (Fuc). The results showed that HPLC-MS/MS pre-column derivatization method was simple and rapid, with small measurement error, but high sensitivity and good repeatability. The analysis of monosaccharide components in polysaccharide components has important practical significance.

[Survey on vitamin A deficiency in children under-6-years in China].

OBJECTIVE: To understand the prevalence and spatial distribution of vitamin A deficiency (VAD) in China among children at ages under six years. METHODS: About 8,600 children under 6 years of age in 14 cities and 28 counties of 14 provinces were selected with stratified cluster sampling for survey, including interview with questionnaire for their family information and nutritional status. Blood specimens were collected for measuring serum level of VA with fluorescent spectrophotometry in laboratory. RESULTS: Totally, 8,669 children under 6 (2,877 in urban area and 5,792 in rural area) were surveyed in 14 provinces, with 4,629 males and 4,040 females. Eight cases of night blindness and seven cases of xerophthalmia were found among the children at ages of two to five years. Sixty-one mothers of the children in this group were also found suffering from night blindness. All the cases of night blindness and xerophthalmia both in children and mothers were living in rural areas. Based on their serum levels of VA, 11.7% of the all 1 018 children were diagnosed as VAD, with serum VA concentrations below or equal to 0.70 micro mol/L. Prevalence of VAD was 15.0% and 5.8% in rural (23.3% in the poverty-stricken counties) and urban areas, respectively, and 5.8%, 11.5% and 16.8% in the coastal, inland and remote areas, respectively. The average serum level of VA was 1.20 micro mol/L and 0.99 micro mol/L for urban and rural areas, respectively, with a national average of 1.06 micro mol/L. And, babies under six months of age with an average serum levels of VA < or = 0.70 micro mol/L accounted for 33.4%, and those at ages of four to five years with the same level of VA accounted for 8%. There was significant difference in serum levels of VA between ages, but no significant difference between genders. CONCLUSION: VAD did exist in children of China, especially in the remote and poverty-stricken rural areas and VA supplementation is urgently needed for the children in these regions.