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The thioether-directed regioselective cycloaddition of internal alkynes with azides was enabled by the in situ generated cationic Ir species, providing modular access to complex S-containing triazoles.

Renal interstitial fibrosis is the common pathological process of various chronic kidney diseases to end-stage renal disease. Inhibition of fibroblast activation attenuates renal interstitial fibrosis. Our previous studies show that poricoic acid A (PAA) isolated from Poria cocos is a potent anti-fibrotic agent. In the present study we investigated the effects of PAA on renal fibroblast activation and interstitial fibrosis and the underlying mechanisms. Renal interstitial fibrosis was induced in rats or mice by unilateral ureteral obstruction (UUO). UUO rats were administered PAA (10 mg·kg−1·d−1, i.g.) for 1 or 2 weeks. An in vitro model of renal fibrosis was established in normal renal kidney fibroblasts (NRK-49F cells) treated with TGF-β1. We showed that PAA treatment rescued Sirt3 expression, and significantly attenuated renal fibroblast activation and interstitial fibrosis in both the in vivo and in vitro models. In TGF-β1-treated NRK-49F cells, we demonstrated that Sirt3 deacetylated β-catenin (a key transcription factor of fibroblast activation) and then accelerated its ubiquitin-dependent degradation, thus suppressing the protein expression and promoter activity of pro-fibrotic downstream target genes (twist, snail1, MMP-7 and PAI-1) to alleviate fibroblast activation; the lysine-49 (K49) of β-catenin was responsible for Sirt3-mediated β-catenin deacetylation. In molecular docking analysis, we found the potential interaction of Sirt3 and PAA. In both in vivo and in vitro models, pharmacological activation of Sirt3 by PAA significantly suppressed renal fibroblast activation via facilitating β-catenin K49 deacetylation. In UUO mice and NRK-49F cells, Sirt3 overexpression enhanced the anti-fibrotic effect of PAA, whereas Sirt3 knockdown weakened the effect. Taken together, PAA attenuates renal fibroblast activation and interstitial fibrosis by upregulating Sirt3 and inducing β-catenin K49 deacetylation, highlighting Sirt3 functions as a promising therapeutic target of renal fibroblast activation and interstitial fibrosis.

Hormones control the reproductive development of Aedes aegypti mosquitoes. The adult male reproductive process and mating behavior require adequate nutrients and energy. Understanding the molecular mechanism linking hormones, energy metabolism, and reproduction in male mosquitoes is important. In this study, we found that the size of the male accessory gland, an essential part of the male reproductive system, gradually increased after eclosion. However, it was significantly reduced in male mosquitoes deficient in methoprene-tolerant (Met), the receptor of juvenile hormone. Likewise, egg hatchability of females that mated with Met-depleted males showed the same downward trend. The mRNA level of the gene encoding accessory gland protein, l-asparaginase (ASNase), was reduced in Met dsRNA-treated males. Electrophoretic mobility shift assay and quantitative reverse transcription-PCR results revealed that Met was capable of binding directly to the promoter of ASNase and activated its transcription. RNA interference of ASNase in males resulted in the reduction of egg hatchability of the females with which they mated. These results showed that Met influenced the fecundity of male mosquitoes by directly upregulating the expression of the ASNase gene. Moreover, the levels of triacylglycerol and the sizes of lipid droplets were decreased by 72-78 h after eclosion in the fat body cells, whereas both of them increased in Met-depleted male mosquitoes, indicating that Met knockdown reduced lipid catabolism. These data demonstrate that Met might influence the egg hatchability of females by regulating lipid metabolism and the development of the male accessory gland in male mosquitoes.

Background The crucial role that nurses play in offering palliative care to patients with life-threatening diseases is widely acknowledged, but the correlation between their eHealth literacy and their knowledge, attitudes, and practice in this domain has yet to be investigated. This study is conducted to investigate the status of eHealth literacy and knowledge, attitudes, and practice regarding palliative care among nurses, and to examine their relationship. Methods A cross-sectional study design was conducted among 546 nurses selected from the first-class tertiary hospitals located both inside and outside of Zhejiang Province between May 12 and May 20, 2022. The online survey of eHealth literacy scale (eHEALS) and scale of knowledge, attitudes, and practice (KAP) regarding palliative care was performed using snowball sampling through the WeChat mini program “Questionnaire Star”. The Spearman rank correlation and binary logistic regression model were used to analyze the independent association between eHealth literacy and KAP toward palliative care. Results The median scores of eHEALS and KAP regarding palliative care were 32 (interquartile range[IQR] 29 to 38) and 82 (IQR 54 to 106) points. The results of correlation analysis showed that the KAP regarding palliative care was significantly correlated with eHEALS (rho = 0.189, P OR = 2.109; P Conclusion Nurses who worked in first-class tertiary hospitals have good levels of eHealth literacy, while the overall level of KAP regarding palliative care is moderate. Our findings highlight that the eHEALS score is independently associated with the KAP score regarding palliative care. Therefore, nursing managers should adopt multiple measures to comprehensively improve eHealth literacy among nurses, further enrich their knowledge of palliative care, promote a positive transformation of attitudes towards palliative care, and efficiently implement palliative care practice, in order to promote high-quality development of palliative care.

To date, the relationship between conjunctivitis and air pollutants has been widely concerned, but the conclusions are not very unified. This study aims to explore the short-term effects of ambient ozone (O3) on the conjunctivitis outpatient visits in Pudong New Area, Shanghai. A quasi-Poisson model combined with the distributed lag nonlinear model (DLNM) was performed to study the short-term effects of O3 on the risk of outpatient visits for conjunctivitis, after controlling the effects of temperature, relative humidity and wind speed. Taking the median concentration of O3 as a reference, the moderate high O3 (75th percentile) showed the largest effect estimates for single and cumulative lag effects at lag 4 (RR 1.013, 95% confidence interval [CI] 1.006–1.019) and lag 0–10 (RR 1.075, 95%CI 1.025–1.128), respectively. Our study suggested that the moderate high O3 increased the chances of conjunctivitis outpatient visits and had an evident lag effect.

In this paper, a novel plate lattice-filled square honeycomb (PLSH) is proposed in an attempt to improve the quasi-static compression performance and energy absorption of structure. Firstly, the quasi-static compression performance of the 3D-printed PLSH was analyzed through experimental investigation and finite element analysis. The results showed that the compressive strength and energy absorption capacity of the proposed PLSHs are higher than the sum of those of square honeycomb (SH) and plate lattices (PLs) which were tested individually. It can be seen that compressive strength per unit mass [Formula: see text] and energy absorption per unit mass [Formula: see text] by 15%–45% and 51%–151% relative to the SH, respectively, and 65.2%–582% and 78%–196% relative to the PLs, respectively. The strengthening mechanism is that the mutual constraint between the SH and PL stabilizes the buckling and alters the compressive deformation mode of both constituents, resulting in elevating compression performance and energy absorption capability of the PLSH.

The first example of transition metal catalyzed asymmetric transformations of the in situ generated p-QMs has been developed, avoiding using pre-synthesized p-QMs requiring bulky 2,6-substitutions.

A rapid construction of 9-arylfluorenes and spirobifluorenes was developed through the tandem Pd-catalysed C–H arylation/demaminative annulation of 1,1-diarylmethylamines with aromatic iodides.

BackgroundPost-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors.MethodsThis study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I2 index were used to evaluate heterogeneity in this meta-analysis.ResultsSix observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90–5.32), anxiety (OR = 3.09, 95% CI = 1.47–6.47), myalgia (OR = 2.33, 95% CI = 1.02–5.33), and hair loss (OR = 2.76, 95% CI = 1.07–7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients.ConclusionThe findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

BACKGROUND AND PURPOSE In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.

Diabetic kidney disease (DKD) is the major complications of type 1 and 2 diabetes, and is the predominant cause of chronic kidney disease and end-stage renal disease. The treatment of DKD normally consists of controlling blood glucose and improving kidney function. The blockade of renin-angiotensin-aldosterone system and the inhibition of sodium glucose cotransporter 2 (SGLT2) have become the first-line therapy of DKD, but such treatments have been difficult to effectively block continuous kidney function decline, eventually resulting in kidney failure and cardiovascular comorbidities. The complex mechanism of DKD highlights the importance of multiple therapeutic targets in treatment. Chinese herbal medicine (active compound, extract and formula) synergistically improves metabolism regulation, suppresses oxidative stress and inflammation, inhibits mitochondrial dysfunction, and regulates gut microbiota and related metabolism via modulating GLP-receptor, SGLT2, Sirt1/AMPK, AGE/RAGE, NF-κB, Nrf2, NLRP3, PGC-1α, and PINK1/Parkin pathways. Clinical trials prove the reliable evidences for Chinese herbal medicine against DKD, but more efforts are still needed to ensure the efficacy and safety of Chinese herbal medicine. Additionally, the ideal combined therapy of Chinese herbal medicine and conventional medicine normally yields more favorable benefits on DKD treatment, laying the foundation for novel strategies to treat DKD.

Tremendous effort has been focused on improving the toughness of epoxy, but the common approaches diminish the mechanical properties. In this work, a new silicone-modified trifunctional epoxy monomer SITEUP is synthesized from the hydrosilylation transformation of eugenol epoxy (EPEU) and tris-(dimethylsiloxy)phenylsilane. The chemical structures and curing kinetics of SITEUP are investigated based on 1H-NMR, 13C-NMR, MADLI-TOF-MS, and DSC analyses. SITEUP is introduced into DGEBA/IPDA systems as a functional modifier in varied loadings for toughening the resulting epoxy thermosets. The impact strength of the modified epoxy thermosets containing 20% SITEUP is 84% higher than that of the pristine epoxy thermoset and also maintains high flexural strength. Further morphology study reveals that the plastic deformation caused by siloxane segments is the key factor accounting for the enhanced toughness of the finalized epoxy thermosets. Si-O-Si segments incorporated into the thermosetting network could absorb more energy by increasing the mobility of polymer chains under external stress and led to improved thermal stability and damping characteristics. In addition, SITEUP is able to decrease the surface tension and increase the hydrophobic properties of the resultant epoxy materials.

With the improvement of industrial automation and technological progress, the number of robots continues to increase, application scenarios are becoming more and more complex, and the requirements for automation and intelligence of robots are also increasing. Due to the development of computer technology and artificial intelligence based on machine vision technical robots has received great attention inthe field of research and production. With the growth of demand, rapid and accurate identification and positioning of objects in any posture in complex spatial environments have become a research hotspot. Based on the image feature processing technology, this paper studies the autonomous target recognition and grasping of industrial robots, establishes the coordinate system of the vision system, derives the projection matrix, and builds a parallel binocular stereo vision system. The method adopted in this paper is that the claw at the end of the robot grips the object to move to different poses, which is used as the theoretical pose of the object, and the grasping result of the visual system is used as the actual pose. The two are compared to solve the grasping errors, a total of 8 comparison experiments were made, and these experimental data were collected and decomposed to draw conclusions. Experiments show that the attitude errors in the X, Y, and Z directions are 1.08°, 1.01°, and 0.92°, respectively. Compared with the previous image positioning errors, it can be found that the errors in the actual robot positioning process are too large, which is mainly caused by the uncalibrated robot; the method used can accurately, quickly, and stably realize the recognition and positioning of the target and meet the needs of the robot for real-time grasping.

Renal interstitial fibrosis (RIF) is the main pathological manifestation of end-stage renal disease. Recent studies have shown that endoplasmic reticulum (ER) stress is involved in the pathogenesis and development of RIF. Traditional Chinese medicine (TCM), as an effective treatment for kidney diseases, can improve kidney damage by affecting the apoptotic signaling pathway mediated by ER stress. This article reviews the apoptotic pathways mediated by ER stress, including the three major signaling pathways of unfolded protein response, the main functions of the transcription factor C/EBP homologous protein. We also present current research on TCM treatment of RIF, focusing on medicines that regulate ER stress. A new understanding of using TCM to treat kidney disease by regulating ER stress will promote clinical application of Chinese medicine and discovery of new drugs for the treatment of RIF.

The aromatic C–H bond etherification with alcohols is one of the most atom-efficient ways to construct aryl ethers. However, it often requires a large excess of alcohols as etherification reagents,...

Background Plasmodium falciparum malaria is recognized as a major global public health problem. The malaria vaccine was important because the case fatality rate of falciparum malaria was high. Plasmodium falciparum circumsporozoite protein (PfCSP) is one of the potential vaccine candidates, but the genetic polymorphism of PfCSP raises concerns regarding the efficacy of the vaccine. This study aimed to investigate the genetic polymorphism of PfCSP and provide data for the improvement of PfCSP-based vaccine (RTS,S malaria vaccine). Methods Blood samples were collected from 287 Chinese migrant workers who were infected with P. falciparum and returning from Africa to Henan Province during 2016–2018. The Pfcsp genes were analysed to estimate the genetic diversity of this parasite. Results The results showed that there were two mutations at the N-terminus of imported Pfcsp in Henan Province, including insertion amino acids (58.71%, 118/201) and A → G (38.81%, 78/201). The number of repeats of tetrapeptide motifs (NANP/NVDP/NPNP/NVDA) in the central repeat region ranged mainly from 39 to 42 (97.51%, 196/201). A total of 14 nonsynonymous amino acid changes were found at the C-terminus. The average nucleotide difference (K) of imported Pfcsp in Henan Province was 5.719, and the haplotype diversity (Hd) was 0.964 ± 0.004. The estimated value of dN-dS was 0.047, indicating that the region may be affected by positive natural selection. The minimum number of recombination events (Rm) of imported Pfcsp in Henan Province was close to that in Africa. The analysis of genetic differentiation showed that there may be moderate differentiation between East Africa and North Africa (Fst = 0.06484), and the levels of differentiation in the other regions were very small (Fst Conclusions The N-terminus of Pfcsp was relatively conserved, and the central repeat region and the Th2R and Th3R regions of the C-terminus were highly polymorphic. The gene polymorphism pattern among Chinese migrant workers returning from Africa to Henan Province was consistent with that in Africa. The geographical pattern of population differentiation and the evidence of natural selection and gene recombination suggested that the effect of polymorphism on the efficacy of PfCSP-based vaccines should be considered.

The internal transcribed spacer (ITS) is one of the most extensively sequenced molecular markers in plant systematics due to its generally concerted evolution. While non-concerted evolution has been found in some plant taxa, such information is missing in Lycium. Molecular studies of six species and two variants of the genus Lycium revealed high levels of intra- and inter-individual polymorphism in the ITS, indicating non-concerted evolution. All genomic DNA ITS paralogues were identified as putative pseudogenes or functional paralogues through a series of comparisons of sequence features, including length and substitution variation, GC content, secondary structure stability, and the presence of conserved motifs in the 5.8S gene, and the rate of evolution. Approximately, 60% of ITS pseudogenes could be easily detected. Based on phylogenetic analysis, all pseudogenes were highly distinct from their corresponding functional copies, tended to evolve neutrally, and clustered randomly together in the evolutionary tree. The results probably suggest that this ITS non-concerted evolution is related to the recent divergence between tandem repeats within the Lycium genome and hybridization between species. Our study complements those of pseudogenes in plant taxa and provides a theoretical basis for the phylogeny and genetic origin of the genus Lycium while having important implications for the use of ITS molecular markers for phylogenetic reconstruction.

The internal transcribed spacer (ITS) is one of the most extensively sequenced molecular markers in plant systematics due to its generally concerted evolution. While non-concerted evolution has been found in some plant taxa, such information is missing in

One Health is a collaborative, multi-sectoral, trans-disciplinary approach with the goal of achieving optimal health outcomes by recognizing the interconnection between people, animals, plants, and the environment and determining how this relates to the control of infectious diseases such as malaria, schistosomiasis and so on. Malarias caused by Plasmodium that commonly infects female Anopheles mosquitoes, which feed on human blood and act as a disease vector. It has been a worldwide important public health problem from ancient times. Also, malaria is one of the infectious diseases with the longest epidemic time and the most serious harm in the history of Henan Province, China. During the past decades, the multi-sectoral, cross-regional, and multi-disciplinary One Health approach contributed to a significant reduction in malaria incidence, resulting in initiation of the Henan Malaria Elimination Action Plan. Herein, we reviewed the history of the fight against malaria in Henan Province. A full picture of malaria epidemics, prevention, and control strategies were showed, with the objective that it will help stakeholders, and policy-makers to take informed decisions on public health issues and intervention designs on malaria control towards elimination in the similar areas.

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity., Cytochrome P450 2A6 (CYP2A6) has an antitumor role and is dramatically downregulated in HCC. CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

Unmanned Aerial Vehicles (UAVs) acting as aerial users to access the cellular network form a promising solution to guarantee its safe and efficient operations via the high-quality communication. Due to the flexible mobility of UAVs and the coverage range limits of ground base station (GBS), the signal-to-noise ratio (SNR) of the communication link between UAVs and GBS will fluctuate. It is an important requirement to maintain the UAV's cellular connection to meet a certain SNR requirement during the mission for UAV flying from take off to landing. In this paper, we study an efficient trajectory planning method that can minimize a cellular-connected UAV's mission completion time under the connectivity requirement. The conventional method to tackle this problem adopts graph theory or a dynamic programming method to optimize the trajectory, which generally incurs high computational complexities. Moreover, there is a non-negligible performance gap compared to the optimal solution. To this end, we propose an iterative trajectory optimizing algorithm based on geometric planning. Firstly, we apply graph theory to obtain all the possible UAV-GBS association sequences and select the candidate association sequences based on the topological relationship among UAV and GBSs. Next, adopting the triangle inequality property, an iterative handover location design is proposed to determine the shortest flight trajectory with fast convergence and low computation complexity. Then, the best flight trajectory can be obtained by comparing all the candidate trajectories. Lastly, we revealed the tradeoff between mission completion time and flight energy consumption. Numerical results validate that our proposed solution can obtain the effectiveness with set accuracy and outperform against the benchmark schemes with affordable computation time.

An organocatalytic enantioselective aza-Michael-Michael-Michael/aldol cyclization quadruple-cascade reaction of 2-amino-β-nitrostyrenes and α,β-unsaturated aldehydes has been developed for the construction of fully substituted hexahydrophenanthridine. This cascade reaction was efficiently catalyzed by diphenylprolinol TMS ether furnishing the tricyclic compounds containing hexahydrophenanthridine bearing five contiguous stereogenic centers with excellent diastereoselectivities (up to >99 : 1 dr) and high to excellent enantioselectivities (up to >99% ee). Application in the gram-scale synthesis of the tricyclic compounds containing hexahydrophenanthridine was also successfully realized.

Using visible light as a driving force and molecular oxygen as a green oxidant, we developed bis(oxazoline)-Ni(acac)2 catalyzed asymmetric α-hydroxylation of β-keto esters under low photosensitizer loading, and the protocol enabled an efficient transformation to provide the desired chiral α-hydroxy-β-keto esters in high yields (up to 99%) and enantioselectivities (up to 99% ee) at room temperature.

The Pd-cataylsed direct ortho-C(sp2)–H fluorination of aromatic ketones has been developed for the first time. The reaction features good regioselectivity and simple operations, constituting an alternative shortcut to access fluorinated ketones. A concise synthesis of anacetrapib has also been achieved by using late-stage C–H fluorination as a key step.

[Cp*IrCl2]2 with a phosphine-free ligand α,α,α-terpyridine shows high catalytic performance in chemodivergent synthesis of α-alkylated arylacetonitriles in the presence of K2CO3 and α-alkylated acetamides in the presence of tBuOK, respectively.

A new and efficient strategy for ring-opening reactions of nitrocyclopropanes is developed for the first time for the divergent synthesis of enynes and enesters via in situ generated highly reactive electron-deficient intermediate allenes. Controllable approaches resulted in enynes and enesters with up to 89% and 90% yields, respectively. The reaction features easy operation, involves green solvents and simple inorganic bases, and is transition-metal free.

An efficient ruthenium-catalyzed method has been developed for the direct N-alkylation of sulfur-containing amines with alcohols, for the first time, by a step-economical and environmentally friendly hydrogen borrowing strategy. The present methodology features base-free conditions and broad substrate scope, with water being the only by-product. Moreover, this protocol has been applied to the synthesis of the pharmaceutical drug Quetiapine.

An efficient Pd-catalysed β-C(sp3)–H arylation of diverse native amides with aryl iodides was developed. This protocol overcomes the necessity of the Thorpe–Ingold effect and features broad substrate scope and good functional group tolerance. The potential application of this protocol is collectively demonstrated by gram-scale synthesis and the synthesis of several bioactive molecules.

Herein, we report a novel strategy to access CH2F-containing ketones through Pd-catalysed β-selective methyl C(sp3)-H fluorination. The reaction features high regioselectivity and a broad substrate scope, constituting a modular method for the late-stage transformation of the native methyl (CH3) into the monofluoromethyl (CH2F) group.

We reviewed the medical records of primary biliary cholangitis patients who were diagnosed by liver biopsy and treated with the corresponding treatment. We evaluated the therapeutic effect and long-term prognostic indicators.This observational cohort study enrolled 80 eligible patients diagnosed by liver biopsy between December 2013 and December 2018 in our department. UDCA monotherapy or UDCA added to prednisolone and immunosuppressant triple therapy was prescribed to patients. We analyzed and compared the demographic characteristics, biochemistry profiles, immune parameters, and noninvasive liver fibrosis assessments at baseline as well as the treatment efficacy, long-term outcomes and adverse effects at baseline and at each visit between the two groups. The indicators that could affect prognosis were assessed.Thirty-eight primary biliary cholangitis patients received UDCA monotherapy (group A), and another 42 patients received UDCA, prednisolone and immunosuppressant triple therapy (group B). After therapy, all patients showed significant improvements in liver biochemical parameters, immune indicators, and noninvasive fibrosis indicators (Fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI)), all P values0.0001. The Mayo score also decreased significantly after treatment (P=0.022). Triple therapy was more effective, and there was a significant difference between the two groups. In addition, multivariate analysis showed that anti-gp210 antibody positivity; antimitochondrial antibody (AMA) negativity; high alkaline phosphatase (ALP), total bilirubin (TBIL) and globulin levels; and a severe degree of fibrosis at baseline were independent predictors of a poor prognosis.Triple therapy was a treatment option for UDCA-refractory PBC patients. Anti-gp210 antibody positivity; AMA negativity; high ALP, TBIL and globulin levels; and a severe degree of fibrosis at baseline were associated with a poor prognosis.

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel–Crafts benzhydrylation of hydroxyindoles with in situ generated ortho-quinome...

Sterols attract increasing attention due to their important bioactivities. The oleaginous yeast Yarrowia lipolytica has large lipid droplets, which provide storage for the accumulated steroid compounds. In this study, we have successfully constructed a campesterol biosynthetic pathway by modifying the synthetic pathway of ergosterol in Y. lipolytica with different capacity of lipid synthesis. The results showed that the maximal campesterol production was produced in the engineered strain YL-D+M−E−, as the optimal lipid content. Furthermore, we found that campesterol mainly exists in the lipid droplets. The campesterol production was further accumulated through the overexpression of two copies of dhcr7. Finally, the maximal campesterol production of 837 mg/L was obtained using a 5-L bioreactor in the engineered YL-D+D+M−E−, exhibiting a 3.7-fold increase compared with the initial strain YL-D+E−. Our results demonstrate that the proper promotion of lipid content plays an important role in campesterol biosynthesis in Y. lipolytica, and what we found provides an effective strategy for the production of hydrophobic compounds. Key Points • Campesterol was biosynthesized by deleting erg5 and introducing heterologous dhcr7. • Campesterol production elevated via promotion of lipid content. • Campesterol was mainly found in lipid droplets. • Promotion of lipid content is an effective strategy to produce hydrophobic compounds.

Background and purpose Increasing evidence has indicated that the high risk of cardiovascular disease in chronic kidney disease (CKD) patients cannot be sufficiently explained by classic risk factors. Experimental approach Based on the least absolute shrinkage and selection operator method, we identified significantly altered renal tissue metabolites during progressive CKD in a 5/6 nephrectomized rat model and in CKD patients. Key results Six aryl-containing metabolites (ACMs) were significantly increased from Week 1 to Week 20. They were associated with the activation of aryl hydrocarbon receptor (AhR) and its target genes including CYP1A1, CYP1A2 and CYP1B1, which were further validated by molecular docking. Our study further demonstrated that AhR signalling could be activated by ACM in patients with idiopathic membranous nephropathy, diabetic nephropathy and IgA nephropathy. Most importantly, 1-aminopyrene (AP) showed strong positive and negative correlation with serum creatinine and creatinine clearance, respectively. AP significantly up-regulated the mRNA expressions of AhR and its three target genes in both mice and NRK-52E cells, while this effect was partially weakened in AhR small hairpin RNA-treated mice and NRK-52E cells. Furthermore, dietary flavonoid supplementation ameliorated CKD and renal fibrosis through partially inhibiting the AhR activity via lowering the ACM levels. The antagonistic effect of flavonoids on AhR was deeply influenced by the number and location of hydroxyl and glycosyl groups. Conclusion and implications We uncovered that endogenous AP is a novel mediator of CKD progression via AhR activation; thus, AhR might serve as a promising target for CKD treatment.

Selective C(sp3)–C(sp2) bond construction is of central interest in chemical synthesis. Despite the success of classic cross-coupling reactions, the cross-dehydrogenative coupling between inert C(s...

A Cu-catalyzed asymmetric 1,6-conjugate addition of

We describe here a Ni-catalysed deamidative fluorination of diverse amides with electrophilic fluorinating reagents. Different types of amides including aromatic amides and olefinic amides were well compatible, affording the corresponding acyl fluorides in good to excellent yields.

Background Epilepsy is a prevalent comorbidity in patients with brain metastases (BM) and could result in sudden and accidental damage, as well as increased disease burden due to its rapid onset. Foreseeing the potential for the development of epilepsy may permit timely and efficient measures. This study aimed to analyze the influencing factors of epilepsy in advanced lung cancer (ALC) patients with BM and construct a nomogram model to predict the likelihood of developing epilepsy. Methods Socio-demographic and clinical data of ALC patients with BM were retrospectively collected from the First Affiliated Hospital of Zhejiang University School of Medicine between September 2019 and June 2021. Univariate and multivariate logistic regression analyses were applied to determine the influencing factors for epilepsy in ALC patients with BM. Based on the results of the logistic regression analysis, a nomogram was built to represent the contribution of each influencing factor in predicting the probability of epilepsy development in ALC patients with BM. The Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve were utilized to evaluate the goodness of fit and prediction performance of the model. Results The incidence of epilepsy among 138 ALC patients with BM was 29.7%. On the multivariate analysis, having a higher number of supratentorial lesions (odds ratio [OR] = 1.727; p = 0.022), hemorrhagic foci (OR = 4.922; p = .021), and a high-grade of peritumoral edema (OR = 2.524; p < .001) were independent risk factors for developing epilepsy, while undergoing gamma knife radiosurgery (OR = .327; p = .019) was an independent protective factor. The p-value of the Hosmer-Lemeshow test was .535 and the area under the ROC curve (AUC) was .852 (95% CI: .807–.897), suggesting the model had a good fit and exhibited strong predictive accuracy. Conclusion The nomogram was constructed that can predict the probability of epilepsy development for ALC patients with BM, which is helpful for healthcare professionals to identify high-risk groups early and allows for individualized interventions.

Ischemia/reperfusion (IR) injury contributes to disability and mortality worldwide. Due to the complicated mechanisms and lack of proper therapeutic targets, few interventions are available that specifically target the pathogenesis of IR injury. Regulated cell death (RCD) of endothelial and parenchymal cells is recognized as the promising intervening target. Recent advances in IR injury suggest that small molecules exhibit beneficial effects on various RCD against IR injury, including apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, and parthanatos. Here, we describe the mechanisms behind these novel promising therapeutic targets and explain the machinery powering the small molecules. These small molecules exert protection by targeting endothelial or parenchymal cells to alleviate IR injury. Therapies of the ideal combination of small molecules targeting multiple cell types have shown potent synergetic therapeutic effects, laying the foundation for novel strategies to attenuate IR injury.

Renal fibrosis is the common and final pathological process of kidney diseases. As a dynamic and reversible post-translational modification, SUMOylation and deSUMOylation of transcriptional factors and key mediators significantly affect the development of renal fibrosis. Recent advances suggest that SUMOylation functions as the promising intervening target against renal fibrosis, and natural products prevent renal fibrosis

Novel high-performance non-labeled fluoro-sensing micro/nano-optics require lithographically fabricable stimuli-fluorescence transductive materials well-tailored in molecular levels, towards superior processibility, stability, sensitivity, on-chip integration and portability, and real-time and in situ analysis. Here, aggregation-induced-emission fluorophores with oxetane groups (AIEoxes) and their covalently co-crosslinkable epoxy composites are customized for the fabrication of micro/nano-devices via single/multi-photon lithography. The oxetane modification increases the AIEoxe miscibility in the epoxy matrix (doping ratio up to 10 wt%), and consequently improves the as-formed devices’ quality, stability, and fluorescence intensity and sensitivity. The multi-color-AIEoxe polymeric micro/nano-devices allow fluorescence-resonance-energy-transfer among AIEoxes, which enables sensitive and specifically spectral detection of VOCs. With the micro/nano-waveguide configuration, solvent-responsive AIE fluorescence and evanescent-field/refractive-index sensing enhance the AIE-fluorescent detection of trace organic solvents in aqueous solutions (detection limit, ∼0.004% v/v, tetrahydrofuran/water) and their facile integration in functional micro/nano-systems like optofluidics.

A nitrate-promoted Pd-catalysed mild cross-dehydrogenative C(sp2)-H bond oxidation of oximes or azobenzenes with diverse carboxylic acids has been developed. In contrast to the previous catalytic systems, this protocol features mild conditions (close to room temperature for most cases) and a broad substrate scope (up to 64 examples), thus constituting a versatile method to directly prepare diverse O-aryl esters. Moreover, the superiority of the nitrate additive in this mild transformation was further determined by experimental and computational evidence.