Layer-Dependent Superconductivity in Iron-Based Superconductors CsCa2Fe4As4F2 and CaKFe4As4.

In the quasi-two-dimensional superconductor NbSe2, the superconducting transition temperature (Tc) is layer-dependent, decreasing by about 60% in the monolayer limit. However, for the extremely anisotropic copper-based high-Tc superconductor Bi2Sr2CaCu2O8+δ (Bi-2212), the Tc of the monolayer is almost identical with that of its bulk counterpart. To clarify the effect of dimensionality on superconductivity, here, we successfully fabricate ultrathin flakes of iron-based high-Tc superconductors CsCa2Fe4As4F2 and CaKFe4As4. It is found that the Tc of monolayer CsCa2Fe4As4F2 (after tuning to the optimal doping by ionic liquid gating) is about 20% lower than that of the bulk crystal, while the Tc of three-layer CaKFe4As4 decreases by 46%, showing a more pronounced dimensional effect than that of CsCa2Fe4As4F2. By carefully examining their anisotropy and the c-axis coherence length, we reveal the general trend and empirical law of the layer-dependent superconductivity in these quasi-two-dimensional superconductors.

Krüppel-like factor 12 regulates aging ovarian granulosa cell apoptosis by repressing SPHK1 transcription and sphingosine-1-phosphate (S1P) production.

Oxidative stress triggered by aging, radiation, or inflammation impairs ovarian function by inducing granulosa cell (GC) apoptosis. However, the mechanism inducing GC apoptosis has not been characterized. Here, we found that ovarian GCs from aging patients showed increased oxidative stress, enhanced reactive oxygen species activity, and significantly decreased expression of the known antiapoptotic factor sphingosine-1-phosphate/sphingosine kinase 1 (SPHK1) in GCs. Interestingly, the expression of Krüppel-like factor 12 (KLF12) was significantly increased in the ovarian GCs of aging patients. Furthermore, we determined that KLF12 was significantly upregulated in hydrogen peroxide-treated GCs and a 3-nitropropionic acid-induced in vivo model of ovarian oxidative stress. This phenotype was further confirmed to result from inhibition of SPHK1 by KLF12. Interestingly, when endogenous KLF12 was knocked down, it rescued oxidative stress-induced apoptosis. Meanwhile, supplementation with SPHK1 partially reversed oxidative stress-induced apoptosis. However, this function was lost in SPHK1 with deletion of the binding region to the KLF12 promoter. SPHK1 reversed apoptosis caused by hydrogen peroxide-KLF12 overexpression, a result further confirmed in an in vitro ovarian culture model and an in vivo 3-nitropropionic acid-induced ovarian oxidative stress model. Overall, our study reveals that KLF12 is involved in regulating apoptosis induced by oxidative stress in aging ovarian GCs and that sphingosine-1-phosphate/SPHK1 can rescue GC apoptosis by interacting with KLF12 in negative feedback.

Superconductivity and Charge-Density-Wave-Like Transition in Th2Cu4As5.

We report the synthesis, crystal structure, and physical properties of a novel ternary compound, Th2Cu4As5. The material crystallizes in a tetragonal structure with lattice parameters a = 4.0639(3) Å and c = 24.8221(17) Å. Its structure can be described as an alternating stacking of fluorite-type Th2As2 layers with antifluorite-type double-layered Cu4As3 slabs. The measurement of electrical resistivity, magnetic susceptibility, and specific heat reveals that Th2Cu4As5 undergoes bulk superconducting transition at 4.2 K. Additionally, all these physical quantities exhibit anomalies at 48 K, accompanied by a sign change in the Hall coefficient, suggesting a charge-density-wave-like (CDW) phase transition. Drawing from both experimental data and band calculations, we propose that the superconducting and CDW-like phase transitions are, respectively, associated with the Cu4As3 slabs and the As plane in the Th2As2 layers.

"UHPLC-Q-TOF/MS-chemometrics-network pharmacology" integrated strategy to discover quality markers of raw and stir-fried Fructus Tribuli and process optimization of stir-fried Fructus Tribuli.

INTRODUCTION: Fructus Tribuli, the dried ripe fruit of Tribulus terrestris L., has various beneficial effects, including liver-calming and depression-relieving effects. Raw Fructus Tribuli (RFT) and stir-fried Fructus Tribuli (SFT) are included in the Chinese Pharmacopoeia 2020 edition (Ch. P 2020). However, owing to the lack of specific regulations on SFT-processing parameters in Ch. P 2020, it is difficult to ensure the quality of commercially available SFT. OBJECTIVE: The present study aimed to screen the quality markers (Q-markers) of RFT and SFT and optimize the processing technology of SFT based on the identified Q-markers. METHODS: First, the ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) technology as well as multiple statistical analysis along with network pharmacology was used to comprehensively identify the Q-markers of RFT and SFT. Then, based on single-factor experiments, the Box-Behnken design (BBD) response surface methodology (RSM) was used to optimize the processing technology of SFT and perform process validation. RESULTS: A total of 63 components were identified in RFT and SFT extracts. Terrestrosin D and Terrestrosin K were initially considered the Q-markers of RFT and SFT, respectively. The optimum processing technology conditions were 208°C, 14 min, and 60 r·min-1. Three batches of process validation were performed, and the mean composite score was 56.87, with a relative standard deviation (RSD) value of 1.13%. CONCLUSION: The content of steroidal saponin components in RFT was significantly different before and after stir-frying. Terrestrosin D and Terrestrosin K were validated as the Q-markers of RFT and SFT, respectively. The identification of Q-markers for RFT and SFT offered a clear index for optimizing the SFT-processing technology and provided a basis for the quality control of RFT and SFT decoction pieces.

[Anti-aging effect and molecular mechanism of Xiyangshen Sanqi Danshen Granules based on metabolomics and bioinformatics].

This study investigated the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules based on metabonomics, network pharmacology, and molecular docking. The aging mice model was induced by intraperitoneal injection of D-galactose(D-gal). Mice were randomly divided into a control group, model group, melatonin group(MT group), and low, medium, and high dose groups of Xiyangshen Sanqi Danshen Granules(XSD-L, XSD-M, and XSD-H). An open-field experiment was conducted, and the expression of cell cycle arrest proteins(p16) and phosphorylated histone family 2A variant(γH2AX) in the brain tissue was detected by immunofluorescence. The expression of interleukin-1ß(IL-1ß) and interleukin-6(IL-6) in the brain tissue was detected by enzyme-linked immunosorbent assay(ELISA). Metabolomics analysis was performed on the serum of mice in control, model, and XSD-H groups to obtain metabolic processes and metabolites. The effective chemical components and potential targets of Xiyangshen Sanqi Danshen Granules were predicted through network pharmacology, and the network diagram of "drug-effective chemical components-key targets" was constructed. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were carried out, and a protein-protein interaction(PPI) network was constructed to clarify the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules. The results showed that the Xiyangshen Sanqi Danshen Granules could significantly improve the aging degree of D-gal mice, significantly improve the total motion distance and the mean motion speed of D-gal mice, and reduce the rest time. In addition, Xiyangshen Sanqi Danshen Granules could significantly reduce the protein levels of IL-6 and IL-1ß and the expression of p16 and γH2AX in D-gal mice. Compared with the model group, 66 differential metabolites(DMs) were significantly up-regulated, and 91 DMs were down-regulated in the XSD-H group. Moreover, four key metabolic pathways(tryptophan metabolism, glycerophospholipid metabolism, pyrimidine metabolism, and lysine degradation) and 16 biomarkers(lysine, tryptophan, indoleacetaldehyde, PCs, LysoPCs, 3-hydroxyanthranilic acid, melatonin, etc) were screened out. 58 main active components and 62 key targets of Xiyangshen Sanqi Danshen Granules were screened by network pharmacology. The GO functional enrichment analysis found the positive regulation of gene expression, drug response, etc. KEGG pathway enrichment screening involved diabetic complications-related AGE-RAGE signaling pathway, hypoxia inducible factor-1 signaling pathway, etc. Through the PPI network and molecular docking, six potential core targets of STAT3, MAPK1, MAPK14, EGFR, FOS, and STAT1 were screened.

Spin-Lattice Coupled Metamagnetism in Frustrated van der Waals Magnet CrOCl.

The long-range magnetic ordering in frustrated magnetic systems is stabilized by coupling magnetic moments to various degrees of freedom, for example, by enhancing magnetic anisotropy via lattice distortion. Here, the unconventional spin-lattice coupled metamagnetic properties of atomically-thin CrOCl, a van der Waals antiferromagnet with inherent magnetic frustration rooted in the staggered square lattice, are reported. Using temperature- and angle-dependent tunneling magnetoconductance (TMC), in complementary with magnetic torque and first-principles calculations, the antiferromagnetic (AFM)-to-ferrimagnetic (FiM) metamagnetic transitions (MTs) of few-layer CrOCl are revealed to be triggered by collective magnetic moment flipping rather than the established spin-flop mechanism, when external magnetic field (H) enforces a lattice reconstruction interlocked with the five-fold periodicity of the FiM phase. The spin-lattice coupled MTs are manifested by drastic jumps in TMC, which show anomalous upshifts at the transition thresholds and persist much higher above the AFM Néel temperature. While the MTs exhibit distinctive triaxial anisotropy, reflecting divergent magnetocrystalline anisotropy of the c-axis AFM ground state, the resulting FiM phase has an a-c easy plane in which the magnetization axis is freely rotated by H. At the 2D limit, such a field-tunable FiM phase may provide unique opportunities to explore exotic emergent phenomena and novel spintronics devices.

Highly Oxygenated Labdane Diterpenoids from Stevia rebaudiana and Their Anti-Atherosclerosis Activities.

Five unknown labdane diterpenoids Stevelins A-E (1-5), three known labdane diterpenoids (6-8) and three labdane norditerpenoids (9-11) were isolated from the Stevia rebaudiana. The structures were determined primarily via NMR spectroscopic data and HR-ESI-MS experiments. X-ray crystallography using CuKα radiation was used to determine the absolute configurations of 1, and the absolute configurations of 2-5 were deduced by electronic circular dichroism (ECD) calculations. The potential anti-atherosclerosis activities of all compounds were evaluated by measuring their inhibitory effects on the macrophage foam cell formation. As a result, most isolated compounds could significantly inhibit oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment for atherosclerosis.

[COL4A5 genotypes and clinical characteristics of children with Alport syndrome]. / 儿童Alport综合征COL4A5åŸºå› åž‹åŠä¸´åºŠç‰¹ç‚¹åˆ†æž.

OBJECTIVES: To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS). METHODS: A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations. RESULTS: Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset. CONCLUSIONS: This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

Electrochemical Ring-Opening Dicarboxylation of Strained Carbon-Carbon Single Bonds with CO2: Facile Synthesis of Diacids and Derivatization into Polyesters.

Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C─C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C─C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy versus Sorafenib for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Randomized Trial.

Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.

Mo3ReRuC: A Noncentrosymmetric Superconductor Formed in the MoReRu-Mo2C System.

A quaternary compound with the composition Mo3ReRuC is obtained in a previously unexplored MoReRu-Mo2C system. According to X-ray structural analysis, Mo3ReRuC crystallizes in the noncentrosymmetric space group P4132 [cubic ß-Mn-type structure, a = 6.8107(1) Å]. Below 7.7 K, Mo3ReRuC becomes a bulk type-II superconductor with an upper critical field close to the Pauli paramagnetic limit. The specific heat data give a large normalized jump ΔCp/γTc = 2.3 at Tc, which points to a strongly coupled superconducting state. First-principles calculations show that its electronic states at the Fermi level are mainly contributed by Mo, Re, and Ru atoms and strongly increased by the spin-orbit coupling. Our finding suggests that the intermediate phase between alloys and carbides may be a good place to look for ß-Mn-type noncentrosymmetric superconductors.

Structure and Physical Properties of the Layered Titanium-Based Pnictide Oxides (EuF)2Ti2Pn2O (Pn = Sb, Bi).

We report two novel titanium-based pnictide oxide compounds (EuF)2Ti2Pn2O (Pn = Sb, Bi), which are synthesized by replacing Sr2+ in (SrF)2Ti2Pn2O [Liu, R. H. Structure and Physical Properties of the Layered Pnictide-Oxides: (SrF)2Ti2Pn2O (Pn = As, Sb) and (SmO)2Ti2Sb2O. Chem. Mater. 2010, 22, 1503-1508] with Eu2+ using a solid-state reaction. (EuF)2Ti2Sb2O exhibits an obvious anomaly in resistivity and heat capacity at T ∼ 195 K, which may arise from the spin-density wave/charge-density wave instability. Similar features are also observed in BaTi2Pn2O, (SrF)2Ti2Pn2O, and Na2Ti2Pn2O (Pn = As and Sb) [Liu, R. H. Structure and Physical Properties of the Layered Pnictide-Oxides: (SrF)2Ti2Pn2O (Pn = As, Sb) and (SmO)2Ti2Sb2O. Chem. Mater. 2010, 22, 1503-1508, Ozawa, T. C. Chemistry of layered d-metal pnictide oxides and their potential as candidates for new superconductors. Sci. Technol. Adv. Mater. 2008, 9, 033003, Wang, X. F. Structure and physical properties for a new layered pnictide-oxide: BaTi2As2O. J. Phys.: Condens. Matter. 2010, 22, 075702, and Xu, H. C. Electronic structure of the BaTi2As2O parent compound of the titanium-based oxypnictide superconductor. Phys. Rev. B 2014, 89, 155108]. Magnetic susceptibility measurements indicate an antiferromagnetic transition at T ∼ 2.5 K for (EuF)2Ti2Sb2O. In particular, the electronic specific heat coefficients of both (EuF)2Ti2Sb2O and (EuF)2Ti2Bi2O are significantly enhanced compared to those of (SrF)2Ti2Pn2O, Na2Ti2Pn2O, and BaTi2Pn2O,1,5,6 which may be due to a strong electron correlation effect in this system. Thus, (EuF)2Ti2Pn2O (Pn = Sb, Bi) may provide new platforms for studying density wave, magnetic ordering, and electron correlation effects.

Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal cancer: a real-world retrospective study.

BACKGROUND: Hepatic arterial infusion chemotherapy delivers the drug directly to the liver. We aim to explore the benefits and tolerability of Hepatic arterial infusion chemotherapy plus regorafenib in advanced colorectal liver metastasis refractory to standard systemic chemotherapy. METHODS: This study analyzed 47 patients treated with hepatic arterial infusion chemotherapy plus regorafenib after standard systemic oxaliplatin and/or irinotecan in combination with bevacizumab or cetuximab between Jan 2017 and Jun 2020. Regorafenib was given for only 3 weeks in a 4-week cycle. RESULTS: Among 47 patients, 32 (68%) were males. The median age was 61 (29-75). With a median follow-up of 22.2 months (3.7-50.7 months). Before Hepatic arterial infusion chemotherapy administration in combination with regorafenib, 34 (72.3%) patients previously received ≥ 2 prior lines of systemic therapy and 37 (78.7%)patients previously received targeted biological treatment (anti-VEGF or anti-EGFR, or both). The initial doses of regorafenib were 40 mg/d (n = 1, 2.13%), 80 mg/d (n = 11, 23.43%), 120 mg/d (n = 2, 4.26%), and 160 mg/d (n = 23, 48.94%), while for 24.6% (n = 14) dose was unknown. Median Overall Survival was 22.2 months. Median Progression-Free Survival was 10.8 (95% CI: 9.0-13.7) months. Common Adverse Events were hand-foot skin reaction (12.77%), fatigue (6.38%), vomiting (6.38%), and decreased appetite (6.38%). Only 2 patients discontinued regorafenib due to Adverse Events. CONCLUSIONS: Regorafenib combined with Hepatic arterial infusion was effective and tolerable in patients with liver predominant metastasis of colorectal cancer. Hence, this therapy can be considered as an alternative for second- or subsequent lines of therapy in patients refractory to standard systemic chemotherapy.

Runoff control simulation and comprehensive benefit evaluation of low-impact development strategies in a typical cold climate area.

With the acceleration of urbanization, the proportion of surface imperviousness is increasing continuously in cities, resulting in frequent waterlogging disasters. In this context, storm water management, based on the low-impact development (LID) concept, offers an effective measure for the management of urban storm waters. First, the storm water management model (SWMM) was built for a typical cold climate city (Changchun) in China. Next, the two-stage calibrated model was employed to explore the surface runoff and storm sewer control effects of four LID combination plans. Finally, these plans were put through a "cost-benefit" evaluation through an analytic hierarchy process. According to the results, after using four LID plans, the reduction rates of peak runoff exceeded 40% and the problem of overflow load of the storm sewage was significantly mitigated. The infiltration-oriented Plan I proved to be the optimal plan, with the lowest proportions of the overflow nodes and full-load pipe sections in each return period, as well as with maximum overall performance. This study offers technical and conformed methodological support to cold cities for the prevention and control of waterlogging disasters and recycling of rainwater resources.

The mechanism and effects of remdesivir-induced developmental toxicity in zebrafish: Blood flow dysfunction and behavioral alterations.

The antiviral drug remdesivir has been used to treat the growing number of coronavirus disease 2019 (COVID-19) patients. However, the drug is mainly excreted through urine and feces and introduced into the environment to affect non-target organisms, including fish, which has raised concerns about potential ecotoxicological effects on aquatic organisms. Moreover, studies on the ecological impacts of remdesivir on aquatic environments have not been reported. Here, we aimed to explore the toxicological impacts of microinjection of remdesivir on zebrafish early embryonic development and larvae and the associated mechanism. We found that 100 µM remdesivir delayed epiboly and impaired convergent movement of embryos during gastrulation, and dose-dependent increases in mortality and malformation were observed in remdesivir-treated embryos. Moreover, 10-100 µM remdesivir decreased blood flow and swimming velocity and altered the behavior of larvae. In terms of molecular mechanisms, 80 differentially expressed genes (DEGs) were identified by transcriptome analysis in the remdesivir-treated group. Some of these DEGs, such as manf, kif3a, hnf1ba, rgn, prkcz, egr1, fosab, nr4a1, and ptgs2b, were mainly involved in early embryonic development, neuronal developmental disorders, vascular disease and the blood flow pathway. These data reveal that remdesivir can impair early embryonic development, blood flow and behavior of zebrafish embryos/larvae, probably due to alterations at the transcriptome level. This study suggests that it is important to avoid the discharge of remdesivir to aquatic ecosystems and provides a theoretical foundation to hinder remdesivir-induced ecotoxicity to aquatic environments.

Inequities in Health Care Services Caused by the Adoption of Digital Health Technologies: Scoping Review.

BACKGROUND: Digital health technologies (ie, the integration of digital technology and health information) aim to increase the efficiency of health care delivery; they are rapidly adapting to health care contexts to provide improved medical services for citizens. However, contrary to expectations, their rapid adoption appears to have led to health inequities, with differences in health conditions or inequality in the distribution of health care resources among different populations. OBJECTIVE: This scoping review aims to identify and describe the inequities of health care services brought about by the adoption of digital health technologies. The factors influencing such inequities, as well as the corresponding countermeasures to ensure health equity among different groups of citizens, were also studied. METHODS: Primary studies and literature, including articles and reviews, published in English between 1990 and 2020 were retrieved using appropriate search strategies across the following three electronic databases: Clarivate Analytics' Web of Science, PubMed, and Scopus. Data management was performed by two authors (RY and WZ) using Thomson Endnote (Clarivate Analytics, Inc), by systematically screening and identifying eligible articles for this study. Any conflicts of opinion were resolved through discussions with the corresponding author. A qualitative descriptive synthesis was performed to determine the outcomes of this scoping review. RESULTS: A total of 2325 studies were collected during the search process, of which 41 (1.76%) papers were identified for further analysis. The quantity of literature increased until 2016, with a peak in 2020. The United States, the United Kingdom, and Norway ranked among the top 3 countries for publication output. Health inequities caused by the adoption of digital health technologies in health care services can be reflected in the following two dimensions: the inability of citizens to obtain and adopt technology and the different disease outcomes found among citizens under technical intervention measures. The factors that influenced inequities included age, race, region, economy, and education level, together with health conditions and eHealth literacy. Finally, action can be taken to alleviate inequities in the future by government agencies and medical institutions (eg, establishing national health insurance), digital health technology providers (eg, designing high-quality tools), and health care service recipients (eg, developing skills to access digital technologies). CONCLUSIONS: The application of digital health technologies in health care services has caused inequities to some extent. However, existing research has certain limitations. The findings provide a comprehensive starting point for future research, allowing for further investigation into how digital health technologies may influence the unequal distribution of health care services. The interaction between individual subjective factors as well as social support and influencing factors should be included in future studies. Specifically, access to and availability of digital health technologies for socially disadvantaged groups should be of paramount importance.

α-Amino Acids and Peptides as Bifunctional Reagents: Carbocarboxylation of Activated Alkenes via Recycling CO2.

Carboxylic acids, including amino acids (AAs), have been widely used as reagents for decarboxylative couplings. In contrast to previous decarboxylative couplings that release CO2 as a waste byproduct, herein we report a novel strategy with simultaneous utilization of both the alkyl and carboxyl components from carboxylic acids. Under this unique strategy, carboxylic acids act as bifunctional reagents in the redox-neutral carbocarboxylation of alkenes. Diverse, inexpensive, and readily available α-AAs take part in such difunctionalizations of activated alkenes via visible-light photoredox catalysis, affording a variety of valuable but otherwise difficult to access γ-aminobutyric acid derivatives (GABAs). Additionally, a series of dipeptides and tripeptides also participate in this photocatalytic carbocarboxylation. Although several challenges exist in this system due to the low concentration and quantitative amount of CO2, as well as unproductive side reactions such as hydrodecarboxylation of the carboxylic acids and hydroalkylation of the alkenes, excellent regioselectivity and moderate to high chemoselectivity are achieved. This process features low catalyst loading, mild reaction conditions, high step and atom economy, and good functional group tolerance, and it is readily scalable. The resulting products are subject to efficient derivations, and the overall process is amenable to applications in the late-stage modification of complex compounds. Mechanistic studies indicate that a carbanion is generated catalytically and it acts as the key intermediate to react with CO2, which is also generated catalytically in situ and thus remains in low concentration. The overall transformation represents an efficient and sustainable system for organic synthesis, pharmaceutics, and biochemistry.

Complete genome sequence and virulence characterization of a neonatal meningitis Escherichia coli isolate.

Neonatal bacterial meningitis is a life-threatening disease in newborns, and neonatal meningitis Escherichia coli (NMEC) is the second most frequent bacteria causing this disease worldwide. In order to further understand the characteristics of this pathogen, an E. coli isolate W224 N from newborns with meningitis was sequenced for detailed genetic characterization and the virulence was tested by a series of phenotypic experiments. W224 N has a circular chromosome and three plasmids. It belongs to ST95 and the serotype is O18:H7. Comparative genomic analysis showed that W224 N was closely related to E. coli neonatal meningitis isolates RS218 and NMEC O18. There are 11 genomic islands in W224 N and most of the GIs are specific to W224 N. W224 N has most of the virulence factors other neonatal meningitis isolates have. The virulence genes located both on the genome and plasmid. At the same time, we found a virulence factor cdiA only present in W224 N but absent in the other five genomes analyzed. In vitro experiment showed that W224 N has strong serum resistance ability, low biofilm formation ability and high flagellar motility. It also has a very strong toxicity to mice and amoeba. The whole genome as well as in vitro and in vivo experiments showed that W224 N is a high virulent strain. The results can help us better learn about the pathogenicity of neonatal meningitis E. coli.

Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study.

BACKGROUND: The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment. METHODS: This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5-7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed. RESULTS: The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1-13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively. CONCLUSIONS: The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.

Sulfate dependent ammonium oxidation: A microbial process linked nitrogen with sulfur cycle and potential application.

Sulfate dependent ammonium oxidation (Sulfammox) is a potential microbial process coupling ammonium oxidation with sulfate reduction under anaerobic conditions, which provides a novel link between nitrogen and sulfur cycle. Recently, Sulfammox was detected in wastewater treatments and was confirmed to occur in natural environments, especially in marine sediments. However, knowledge gaps in the mechanism of Sulfammox, functional bacteria, and their metabolic pathway, make it challenging to estimate its environmental significance and potential applications. This review provides an overview of recent advances in Sulfammox, including possible mechanisms, functional bacteria, and main influential factors, and discusses future challenges and opportunities. Future perspectives are outlined and discussed, such as exploration of microbial community structure and metabolic pathways, possible interactions with other microbes, environmental significance, and potential applications for nitrogen and sulfate removal, to inspire more researches on the Sulfammox process.