Epigenetic silencing of LDHB promotes hepatocellular carcinoma by remodeling the tumor microenvironment.

Lactate dehydrogenase B (LDHB) reversibly catalyzes the conversion of pyruvate to lactate or lactate to pyruvate and expressed in various malignancies. However, the role of LDHB in modulating immune responses against hepatocellular carcinoma (HCC) remains largely unknown. Here, we found that down-regulation of lactate dehydrogenase B (LDHB) was coupled with the promoter hypermethylation and knocking down the DNA methyltransferase 3A (DNMT 3A) restored LDHB expression levels in HCC cell lines. Bioinformatics analysis of the HCC cohort from The Cancer Genome Atlas revealed a significant positive correlation between LDHB expression and immune regulatory signaling pathways and immune cell infiltrations. Moreover, immune checkpoint inhibitors (ICIs) have shown considerable promise for HCC treatment and patients with higher LDHB expression responded better to ICIs. Finally, we found that overexpression of LDHB suppressed HCC growth in immunocompetent but not in immunodeficient mice, suggesting that the host immune system was involved in the LDHB-medicated tumor suppression. Our findings indicate that DNMT3A-mediated epigenetic silencing of LDHB may contribute to HCC progression through remodeling the tumor immune microenvironment, and LDHB may become a potential prognostic biomarker and therapeutic target for HCC immunotherapy.

A systematic mutation analysis of 13 major SARS-CoV-2 variants.

SARS-CoV-2 evolves constantly with various novel mutations. Due to their enhanced infectivity, transmissibility and immune evasion, a comprehensive understanding of the association between these mutations and the respective functional changes is crucial. However, previous mutation studies of major SARS-CoV-2 variants remain limited. Here, we performed systematic analyses of full-length amino acids mutation, phylogenetic features, protein physicochemical properties, molecular dynamics and immune escape as well as pseudotype virus infection assays among thirteen major SARS-CoV-2 variants. We found that Omicron exhibited the most abundant and complex mutation sites, higher indices of hydrophobicity and flexibility than other variants. The results of molecular dynamics simulation suggest that Omicron has the highest number of hydrogen bonds and strongest binding free energy between the S protein and ACE2 receptor. Furthermore, we revealed 10 immune escape sites in 13 major variants, some of them were reported previously, but four of which (i.e. 339/373/477/496) are first reported to be specific to Omicron, whereas 462 is specific to Epslion. The infectivity of these variants was confirmed by the pseudotype virus infection assays. Our findings may help us understand the functional consequences of the mutations within various variants and the underlying mechanisms of the immune escapes conferred by the S proteins.

Engineering a Carotenoid Cleavage Oxygenase for Coenzyme-Free Synthesis of Vanillin from Ferulic Acid.

One-pot biosynthesis of vanillin from ferulic acid without providing energy and cofactors adds significant value to lignin waste streams. However, naturally evolved carotenoid cleavage oxygenase (CCO) with extreme catalytic conditions greatly limited the above pathway for vanillin bioproduction. Herein, CCO from Thermothelomyces thermophilus (TtCCO) was rationally engineered for achieving high catalytic activity under neutral pH conditions and was further utilized for constructing a one-pot synthesis system of vanillin with Bacillus pumilus ferulic acid decarboxylase. TtCCO with the K192N-V310G-A311T-R404N-D407F-N556A mutation (TtCCOM3) was gradually obtained using substrate access channel engineering, catalytic pocket engineering, and pocket charge engineering. Molecular dynamics simulations revealed that reducing the site-blocking effect in the substrate access channel, enhancing affinity for substrates in the catalytic pocket, and eliminating the pocket's alkaline charge contributed to the high catalytic activity of TtCCOM3 under neutral pH conditions. Finally, the one-pot synthesis of vanillin in our study could achieve a maximum rate of up to 6.89 ± 0.3 mM h-1. Therefore, our study paves the way for a one-pot biosynthetic process of transforming renewable lignin-related aromatics into valuable chemicals.

Modular Synthesis of Fluoro-Substituted Furan Compounds via Controllable Fluorination of Biomass-Based 5-HMF and Its Derivatives.

5-Hydroxymethylfurfural (5-HMF) is regarded as one of the most promising platform feedstocks for producing valuable chemicals, fuels, and materials. In this study, we present a controllable fluorination technique for biomass-based 5-HMF and its oxygenated derivatives. This technique allows us to synthesize mono-fluoromethyl, difluoromethyl, and acylfluoro-substituted furan compounds by adjusting experimental conditions such as different fluorine sources and mole ratio. To gain a deeper understanding the reactivity order, we conducted intermolecular and intramolecular competition experiments. The results revealed that the hydroxyl group exhibited the highest reactivity, followed by the aldehyde group. This finding provides important theoretical support and opens up the possibility of selective fluorination. The reaction offers several advantages, including mild conditions, no need for inert gas protection, and easy operation. Furthermore, the fluoro-substituted furan compounds can be further transformed for the preparation of drug analogs, offering a new route for the high-value utilization of biomass molecules.

Integrin αvß1 facilitates ACE2-mediated entry of SARS-CoV-2.

Integrins have been suggested to be involved in SARS-CoV-2 infection, but the underlying mechanisms remain largely unclear. This study aimed to investigate how integrins facilitate the ACE2-mediated cellular entry of SARS-CoV-2. We first tested the susceptibility of a panel of human cell lines to SARS-CoV-2 infection using the spike protein pseudotyped virus assay and examined the expression levels of integrins in these cell lines by qPCR, western blot and flow cytometry. We found that integrin αvß1 was highly enriched in the SARS-CoV-2 susceptible cell lines. Additional studies demonstrated that RGD (403-405)→AAA mutant was defective in binding to integrin αvß1 compared to its wild type counterpart, and anti-αvß1 integrin antibodies significantly inhibited the entry of SARS-CoV-2 into the cells. Further studies using mouse NIH3T3 cells expressing human ACE2, integrin αv, integrin ß1, and/or integrin αvß1 suggest that integrin αvß1 was unable to function as an independent receptor but could significantly facilitate the cellular entry of SASR-CoV-2. Finally, we observed that the Omicron exhibited a significant increase in the ACE2-mediated viral entry. Our findings may enhance our understanding of the pathogenesis of SARS-CoV-2 infection and offer potential therapeutic target for COVID-19.

Insights into the regulatory role of bacterial sncRNA and its extracellular delivery via OMVs.

Small noncoding RNAs (sncRNAs) play important regulatory roles in bacterial physiological processes and host-pathogen interactions. Meanwhile, bacterial outer membrane vesicles (OMVs), as naturally secreted outer membrane structures, play a vital role in the interaction between bacteria and their living environment, including the host environment. However, most current studies focus on the biological functions of sncRNAs in bacteria or hosts, while neglecting the roles and regulatory mechanisms of the OMVs that encapsulate these sncRNAs. Therefore, this review aims to summarize the intracellular regulatory roles of bacterial sncRNAs in promoting pathogen survival by regulating virulence, modulating bacterial drug resistance, and regulating iron metabolism, and their extracellular regulatory function for influencing host immunity through host-pathogen interactions. Additionally, we introduce the key role played by OMVs, which serve as important cargoes in bacterial sncRNA-host interactions. We propose emerging pathways of sncRNA action to further discuss the mode of host-pathogen interactions, highlighting that the inhibition of sncRNA delivery by OMVs may prevent the occurrence of infection to some extent. Hence, this review lays the foundation for future prophylactic treatments against bacterial infections and strategies for addressing bacterial drug resistance. KEY POINTS: •sncRNAs have intracellular and extracellular regulatory functions in bacterial physiological processes and host-pathogen interactions. •OMVs are potential mediators between bacterial sncRNAs and host cells. •OMVs encapsulating sncRNAs have more potential biological functions.

Palladium-Catalyzed Cross-Coupling of gem-Difluorocyclopropanes with gem-Diborylalkanes for the Synthesis of Boryl-Substituted Fluorinated Alkenes.

This study presents a novel method for the regioselective coupling of gem-difluorinated cyclopropanes with gem-diborylmethane, utilizing a Pd-catalyst system. This innovative approach enables the synthesis of 2-fluoroalkenyl monoboronate scaffolds with high Z-selectivity. The resulting products undergo further transformations, including oxidation, Suzuki cross-coupling, and trifluoroborylation, all of which are achieved with good yields. This work introduces a valuable synthetic pathway to access important fluorinated compounds for various applications in organic chemistry.

Growth and development of syphilis-exposed and -unexposed uninfected children during their first 18 months of life in Suzhou, China: a nested case-control study with propensity score matching.

Background: With the successful implementation of Prevention of Mother-to-Child Transmission (PMTCT) policies, the proportion of infants with exposure to both syphilis and antibiotic medication in utero has increased in China, but there is limited evidence about the early growth and development of such infants. Methods: We conducted a retrospective nested case-control study based on data from the China PMTCT program conducted in Suzhou from 2016 to 2021. Propensity score matching (PSM) was employed to extract 826 syphilis-exposed but uninfected (SEU) infants and 1,652 syphilis-unexposed uninfected (SUU) infants from a total of 712,653 infants. Maternal characteristics were collected through questionnaires, such as parity, age, education level, smoking and drinking habits during pregnancy. Infantile characteristics were retrieved from medical records or via questionnaires, such as gestational age, gender, mode of delivery, Apgar scores, birth weight and length, outdoor time, vitamin D intake, and feed pattern. Mixed effects models, adjusting for potential influencing factors, were used to investigate the early infantile growth pattern of SEU and SUU infants. All statistical analysis were conducted using R (version 4.2.0). Results: Length and weight were slightly higher in SEU infants than in the SUU infants at some time points (months 0 and 18 for length, p-values <0.05; months 0, 6, and 18 for weight, p < 0.05). In the mixed effects model, SEU group was found to be associated with higher weight [exponentiated beta exp.(ß) = 1.15, 95% Confidence Interval (CI) = 1.06, 1.25], length [exp(ß) = 1.42, 95% CI = 1.14, 1.77], and BMI z-score [exp(ß) = 1.09, 95% CI = 1.00, 1.19]. Conclusion: With the effective prevention of congenital syphilis under the PMTCT program, SEU infants have non-inferior growth patterns during their first 18 months of life compared with SUU controls in Suzhou, China.

Recombinant outer membrane vesicles delivering eukaryotic expression plasmid of cytokines act as enhanced adjuvants against Helicobacter pylori infection in mice.

The widespread prevalence of Helicobacter pylori (H. pylori) infection remains a great challenge to human health. The existing vaccines are not ideal for preventing H. pylori infection; thus, exploring highly effective adjuvants may improve the immunoprotective efficacy of H. pylori vaccines. In a previous study, we found that the outer membrane vesicles (OMVs), a type of nanoscale particle spontaneously produced by Gram-negative bacteria, could act as adjuvants to boost the immune responses to vaccine antigens. In this study, we explored the potential application of OMVs as delivery vectors for adjuvant development. We constructed recombinant OMVs containing eukaryotic expression plasmid of cytokines, including interleukin 17A or interferon-γ, and evaluated their function as adjuvants in combination with inactivated whole-cell vaccine (WCV) or UreB as vaccine antigens. Our results showed that recombinant OMVs as adjuvants could induce stronger humoral and mucosal immune responses in mice than wild-type H. pylori OMVs and the cholera toxin (CT) adjuvant. Additionally, the recombinant OMVs significantly promoted Th1/Th2/Th17-type immune responses. Furthermore, the recombinant OMV adjuvant induced more potent clearance of H. pylori than CT and wild-type OMVs. Our findings suggest that the recombinant OMVs coupled with cytokines may become potent adjuvants for the development of novel and effective vaccines against H. pylori infection.

Effects of the Degree of Phenol Substitution on Molecular Structures and Properties of Chitosan-Phenol-Based Self-Healing Hydrogels.

Click chemistry is commonly used to prepare hydrogels, and chitosan-phenol prepared by using a Schiff base has been widely employed in the field of biomaterials. Chitosan-phenol is a derivative of chitosan; the phenol groups can disrupt both the inter- and intramolecular hydrogen bonds in chitosan, thereby reducing its crystallinity and improving its water solubility. In addition, chitosan-phenol exhibits various beneficial physiological functions. However, it is still unclear whether the degree of phenol substitution in the chitosan main chain affects the molecular interactions and structural properties of the self-healing hydrogels. To explore this issue, we investigated the molecular structure and network of self-healing hydrogels composed of chitosan-phenol with varying degrees of phenol substitution and dibenzaldehyde poly(ethylene oxide) (DB-PEO) using molecular dynamics simulations. We observed that when the degree of phenol substitution in the self-healing hydrogel was less than 15%, an increase in the degree of phenol substitution led to an increase in the interactions between chitosan-phenol and DB-PEO, and it enhanced the dynamic covalent bond cross-linking generated through the Schiff base reaction. However, when the degree of phenol substitution exceeded 15%, excessive phenol groups caused excessive intramolecular interactions within chitosan-phenol molecules, which reduced the binding between chitosan-phenol and DB-PEO. Our results revealed the influence of the degree of phenol substitution on the molecular structure of the self-healing hydrogels and showed an optimal degree of phenol substitution. These findings provide important insights for the future design of self-healing hydrogels based on chitosan and should help in enhancing the applicability of hydrogels in the field of biomedicine.

Tunable Synthesis of Monofluoroalkenes and Gem-Difluoroalkenes via Solvent-Controlled Rhodium-Catalyzed Arylation of 1-Bromo-2,2-difluoroethylene.

Divergent synthesis of fluorine-containing scaffolds starting from a suite of raw materials is an intriguing topic. Herein, we report the solvent-controlled rhodium-catalyzed tunable arylation of 1-bromo-2,2-difluoroethylene. The selection of the reaction solvents provides switchable defluorinated or debrominated arylation from readily available feedstock resources (both arylboronic acids/esters and 1-bromo-2,2-difluoroethylene are commercially available). This switch is feasible because of the difference in coordination ability between the solvent (CH2 Cl2 or CH3 CN) and the rhodium center, resulting in different olefin insertion. This protocol allows the convenient synthesis of monofluoroalkenes and gem-difluoroalkenes, both of which are important scaffolds in the fields of medicine and materials. Moreover, this newly developed solvent-regulated reaction system can be applied to the site-selective dechlorinated arylation of trichloroethylene. Overall, this study provides a useful strategy for the divergent synthesis of fluorine-containing scaffolds and provides insight into the importance of solvent selection in catalytic reactions.

Prevalence and human papillomavirus (HPV) genotype distribution in Suzhou, China.

Persistent infection with high-risk human papillomavirus (HR-HPV) is a known pathogenic factor of cervical cancer. To develop scientific guidance for cervical cancer screening and HPV vaccination, we analyzed HPV genotypes in Suzhou City, China. This study utilized data from the cervical cancer screening project in Suzhou from 2016 to 2021. A total of 444,471 female residents who voluntarily underwent HPV testing were included in the study. The overall HR-HPV prevalence was 10.2%. The three most common HR-HPV genotypes were HPV52 (2.81%), HPV58 (1.64%), and HPV16 (1.46%). The rate of HPV infection increased with age. Having a junior school education or higher was a protective factor compared to having an education level below junior school. The overall HPV infection rate showed a downwards trend from 2016 to 2021. HPV16 exhibited the fastest annual decline rate, followed by HPV18. As the severity of cervical intraepithelial neoplasia increases, the detection rate of HPV infection significantly increased. In conclusion, in addition to cervical cancer screening, it is important to pay attention to health promotion and education for low-educated women aged 45-59. Considering the distribution of HPV genotypes, prioritizing the administration of high-valency HPV vaccines to local seventh-grade female students is recommended.

Surface-Controlled CdS/Ti3 C2 MXene Schottky Junction for Highly Selective and Active Photocatalytic Dehydrogenation-Reductive Amination.

Photocatalytic valorization and selective transformation of biomass-derived platform compounds offer great opportunities for efficient utilization of renewable resources under mild conditions. Here, the novel three-dimensional hierarchical flower-like CdS/Ti3 C2 Schottky junction (MCdS) composed of surface-controlled CdS and pretreated Ti3 C2 MXene is created for photocatalytic dehydrogenation-reductive amination of biomass-derived amino acid production under ambient temperature with unprecedented activity and selectivity. Schottky junction efficiently promotes photoexcited charge migration and separation and inhibits photogenerated electron-hole recombination, which results in a super-high activity. Meanwhile, CdS with the reduced surface energy supplies sufficient hydrogen sources for imine reduction and induces the preferential orientation of alanine, thus contributing superior selectivity. Moreover, a wide range of hydroxyl acids are successfully converted into corresponding amino acids and even one-pot conversion of glucose to alanine is easily achieved over MCdS. This work illustrates the mechanism of crystal orientation control and heterojunction construction in controlling catalytic behavior of photocatalytic nanoreactor, providing a paradigm for construction of MXene-based heterostructure.

GlycoNote with Iterative Decoy Searching and Open-Search Component Analysis for High-Throughput and Reliable Glycan Spectral Interpretation.

Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.

Fabrication of a novel antioxidant emulsifier through tuning the molecular interaction between soy protein isolates and young apple polyphenols.

Soy protein isolates (SPI) exhibit weaker emulsifying properties than those of animal proteins, thereby limiting their wide applicability. In this study, a novel plant-based antioxidant emulsifier was developed using SPI and young apple polyphenols (YAP), and its underlying interaction mechanisms were discovered using multispectral technology and molecular docking. YAP physically bound to SPI through hydrogen bonds and hydrophobic interactions, which significantly enhanced the free radicals scavenging, reducing, and metal ion chelating abilities of SPI by introducing free hydroxyl groups. Moreover, SPI modified by YAP exerted better emulsifying performance owing to a looser protein structure, reflected by a higher random coil and a lower α-helix content. In addition, YAP may bridge adjacent SPI molecules, promoting the adsorption and anchoring of SPI at the oil-water interface. SPI-YAP complexes are promising antioxidant emulsifiers that can be used to nano-deliver functional oils and nutrients, thereby broadening SPI and YAP applications in the food industry.

Photocatalytic Alkyl Radical Addition Tandem Oxidation of Alkenyl Borates.

Photocatalytic oxidation is a popular transformation way for organic synthesis and is widely applied in academia and industry. Herein, we report a blue light-induced alkylation-oxidation tandem reaction for the synthesis of diverse ketones by combining alkyl radical addition and oxidation of alkenyl borates. This reaction shows excellent functional group compatibility in acceptable yields, and diversity of radical precursors is applicable.

The risks of low hemoglobin deferral in a large retrospective cohort of plasmapheresis donors and the influence factors of return for a subsequent donation in China.

Background: According to the Technical Operation Procedures for Plasmapheresis Collection Station (2019) in China, plasmapheresis donors with low hemoglobin (Hb) levels (men <12.0 g/dL; women <11.0 g/dL) were deferred for at least 2 weeks. The purpose of this retrospective study was to survey the demographic characteristics of plasmapheresis donors with low Hb deferral (LHD) and identify at-risk LHD donors, so as to enhance donor safety and improve donation service management. Methods: From 2018 to 2020, a multi-center study involving plasmapheresis donors from 18 plasmapheresis centers in three provinces (Sichuan, Yunnan and Hunan) of China was conducted. Donor demographics (age, sex) and donation information (date of donation, first-time donors vs. repeat donors, the number of lifetime donations, the number of donations in the last 12 months, and whether the LHD donor returned for a subsequent donation) were collected. The Cochran-Mantel-Haenszel method was used to explore the risk factors for LHD while adjusting for the different provinces. Logistic regression analysis was used to investigate the factors influencing the return for a subsequent donation after LHD. Results: A total of 497,039 plasmapheresis donors were included. Female donors' LHD rate was 0.15% on average, while male donors' LHD rate was 0.01%. Female donors aged 41-50 years old (OR: 2.276, 95% CI [1.333-3.887], p = 0.002) were more likely to experience LHD temporarily than those aged 18-30 years old. For female donors, compared with donations in the winter, they had a higher risk for LHD in the summer (OR: 2.217, 95% CI [1.670-2.943], p < 0.001), spring (OR: 2.402, 95% CI [1.806-3.196], p < 0.001), and fall (OR: 2.002, 95% CI [1.500-2.673], p < 0.001). Among the LHD donors, those who had donated more frequently in the past were more likely to return for a subsequent donation (p = 0.012). Conclusions: Female donors were at a higher risk of LHD, particularly between the ages of 41 and 50. A clear seasonal pattern in the rate of LHD was observed. In the winter, the risk of LHD was the lowest; thus, it was advised to recruit plasmapheresis donors throughout the winter and to make the required adjustments for recruitment measures during other seasons. The number of previous donations was correlated with the return rate after LHD. Our observations could have practical implications for plasmapheresis donor management.

Injectable Temperature-Sensitive Hydrogel Loaded with IL-36Ra for the Relief of Osteoarthritis.

Osteoarthritis (OA) is an inflammatory disease accompanied by synovial joint inflammation, and IL-36 plays an important role in this process. Local application of IL-36 receptor antagonist (IL-36Ra) can effectively control the inflammatory response, thereby protecting cartilage and slowing down the development of OA. However, its application is limited by the fact that it is rapidly metabolized locally. We designed and prepared a temperature-sensitive poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel (IL-36Ra@Gel) system carrying IL-36Ra and evaluated its basic physicochemical characteristics. The drug release curve of IL-36Ra@Gel indicated that this system could slowly release the drug over a longer period. Furthermore, degradation experiments showed that it could be largely degraded from the body within 1 month. The biocompatibility-related results showed that it had no significant effect on cell proliferation compared to the control group. In addition, the expression of MMP-13 and ADAMTS-5 was lower in IL-36Ra@Gel-treated chondrocytes than in the control group, and the opposite results appeared in aggrecan and collagen X. After 8 weeks of treatment with IL-36Ra@Gel by joint cavity injection, HE and Safranin O/Fast green staining showed that the degree of cartilage tissue destruction in the IL-36Ra@Gel-treated group was less than those in other groups. Meanwhile, the joints of mice in the IL-36Ra@Gel group had the most intact cartilage surface, the smallest thickness of cartilage erosion, and the lowest OARSI and Mankins score among all groups. Consequently, the combination of IL-36Ra and PLGA-PLEG-PLGA temperature-sensitive hydrogels can greatly improve the therapeutic effect and prolong the drug duration time, thus effectively delaying the progression of degenerative changes in OA, providing a new feasible nonsurgical treatment for OA.

Transmission Pattern of Measles Virus Circulating in China During 1993-2021: Genotyping Evidence Supports That China Is Approaching Measles Elimination.

BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.

Synthesis of conjugated bisallenes by cooperative Cu/Pd-catalysed borylallenylation of 2-trifluoromethyl-1,3-enynes.

A cooperative Cu/Pd-catalysed borylallenylation of 2-trifluoromethyl-1,3-enynes with propargylic carbonates under mild reaction conditions was developed. This method provides facile and efficient access to conjugated bisallenes with a broad range of functional groups. Both aromatic and aliphatic 1,3-enynes can be utilized in this transformation to give the corresponding multi-substituted conjugated bisallenes.