sccomp: Robust differential composition and variability analysis for single-cell data.

Cellular omics such as single-cell genomics, proteomics, and microbiomics allow the characterization of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to revealing markers of disease progression, such as cancer and pathogen infection. A dedicated statistical method for differential variability analysis is lacking for cellular omics data, and existing methods for differential composition analysis do not model some compositional data properties, suggesting there is room to improve model performance. Here, we introduce sccomp, a method for differential composition and variability analyses that jointly models data count distribution, compositionality, group-specific variability, and proportion mean-variability association, being aware of outliers. sccomp provides a comprehensive analysis framework that offers realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies, highlighting the inadequacy of the very popular Dirichlet-multinomial distribution. We show that sccomp accurately fits experimental data, significantly improving performance over state-of-the-art algorithms. Using sccomp, we identified differential constraints and composition in the microenvironment of primary breast cancer.

Mapping the Acetylamino and Carboxyl Groups on Glycans by Engineered α-Hemolysin Nanopores.

Glycan is a crucial class of biological macromolecules with important biological functions. Functional groups determine the chemical properties of glycans, which further affect their biological activities. However, the structural complexity of glycans has set a technical hurdle for their direct identification. Nanopores have emerged as highly sensitive biosensors that are capable of detecting and characterizing various analytes. Here, we identified the functional groups on glycans with a designed α-hemolysin nanopore containing arginine mutations (M113R), which is specifically sensitive to glycans with acetamido and carboxyl groups. Molecular dynamics simulations indicated that the acetamido and carboxyl groups of the glycans produce unique electrical signatures by forming polar and electrostatic interactions with the M113R nanopores. Using these electrical features as the fingerprints, we mapped the length of the glycans containing acetamido and carboxyl groups at the monosaccharide, disaccharide, and trisaccharide levels. This proof-of-concept study provides a promising foundation for developing single-molecule glycan fingerprinting libraries and demonstrates the capability of biological nanopores in glycan sequencing.

Development and application of a low-priced duplex quantitative PCR assay based on SYBR Green I for the simultaneous detection of porcine deltacoronavirus and porcine sapelovirus.

Porcine deltacoronavirus (PDCoV) and porcine sapelovirus (PSV) are two viruses that can cause diarrhoea in pigs and bring great economic loss to the pig industry. In this research, a duplex real-time quantitative polymerase chain reaction (qPCR) assay based on SYBR Green I was developed to simultaneously detect PDCoV and PSV. No specific melting peaks were found in other porcine diarrhoea-associated viruses, indicating that the method developed in this study had good specificity. The detection limits of PDCoV and PSV were 1.0 × 101 copies µl-1 and 1.0 × 102 copies µl-1, respectively. The duplex real-time qPCR assay tested two hundred and three (203) intestinal and faecal samples collected from diarrhoeal and asymptomatic pigs. The positive rates of PDCoV and PSV were 20.2% and 23.2%, respectively. The co-infection rate of PDCoV and PSV was 13.8%. To evaluate the accuracy of the developed method, conventional PCR and singular TaqMan real-time qPCR assays for PDCoV/PSV were also used to detect the samples. The results showed that the duplex real-time qPCR assay was consistent with the singular assays, but its sensitivity was higher than conventional PCR methods. This duplex real-time qPCR assay provides a rapid, sensitive and reliable method in a clinic to simultaneously detect PDCoV and PSV.

Detection and genetic characteristics of porcine circovirus type 2 and 3 in Henan province of China.

PCV2 is one of the most economically important viral agents in swine worldwide. Recently, PCV3 has been frequently reported, and the co-infection of PCV2 and PCV3 is common in China. In order to explore the distribution, epidemiology and genetic diversity of PCV2 and PCV3, a total of 1,760 clinical tissue samples were randomly collected from 18 different regions in Henan province of China from October 2018 to September 2019 and screened for the presence of PCV2 and PCV3 by a duplex real-time PCR assay. The results showed that the positive rates of PCV2 and PCV3 were 72.90% and 5.17% respectively, and the co-infection rate of the two viruses was 3.64%. PCV2 and PCV3 are prevalent all year round. The prevalence of PCV2 in diseased pigs was 83.98%, higher than that in slaughterhouse pigs, while the prevalence of PCV3 in diseased pigs was 2.16%, slightly lower than that in slaughterhouse pigs. Furthermore, the complete genomes of 14 PCV2 and 3 PCV3 strains were obtained, among which 1 belonged to PCV2a, 5 belonged to PCV2b and 8 belonged to PCV2d. A new variant strain (XX2) might escape the host immune system. The phylogenetic analysis of PCV3 showed high nucleotide identity (>98%) between sequences obtained in this study and reference sequences. The results of this study might enrich the epidemiological data of PCV2 and PCV3 in Henan province and provide reference information for the comprehensive prevention and control of PCVAD.

Effects of communication style, anthropomorphic setting and individual differences on older adults using voice assistants in a health context.

BACKGROUND: Voice assistants enable older adults to communicate regarding their health as well as facilitate ageing in place. This study investigated the effects of communication style, anthropomorphic setting, and individual differences on the trust, acceptance, and mental workload of older adults using a voice assistant when communicating health issues. METHODS: This is a mixed-methods study utilising both quantitative and qualitative methods. One hundred and six older adults (M = 71.8 years, SD = 4.6 years) participated in a 2 (communication style: social- vs. task-oriented; between-subject)[Formula: see text] 2 (anthropomorphic setting: ordinary profession vs. medical background; within-subject) mixed design experiment. The study used multivariate analysis of variance (MANOVA) to examine the effects of communication style, anthropomorphic setting of the voice assistant, and participants' use frequency of digital devices on the trust, technology acceptance, and mental workload of older adults using a voice assistant in a health context. End-of-study interviews regarding voice assistant use were conducted with participants. Qualitative content analyses were used to assess the interview findings about the communication content, the more trustworthy anthropomorphic setting, and suggestions for the voice assistant. RESULTS: Communication style, anthropomorphic setting, and individual differences all had statistically significant effects on older adults' evaluations of the voice assistant. Compared with a task-oriented voice assistant, older adults preferred a social-oriented voice assistant in terms of trust in ability, integrity, and technology acceptance. Older adults also had better evaluations for a voice assistant with a medical background in terms of trust in ability, integrity, technology acceptance, and mental workload. In addition, older adults with more experience using digital products provided more positive evaluations in terms of trust in ability, integrity, and technology acceptance. CONCLUSIONS: This study suggests that when designing a voice assistant for older adults in the health context, using a social-oriented communication style and providing an anthropomorphic setting in which the voice assistant has a medical background are effective ways to improve the trust and acceptance of older adults of voice assistants in an internet-of-things environment.

Experimental and theoretical research on the effect of coupling heat and pH on the structure and antioxidant activity of cyanidin-3-O-glucoside from black soybean coat.

BACKGROUND: Since anthocyanin has good coloration and antioxidant properties, many studies have focused on exploring the stability and antioxidant activity of anthocyanin. The objective of this work was to study effects of pH and temperature on the bioactivity of cyanidin-3-O-glucoside (C3G) and ultra-performance liquid chromatography-photodiode array-electrospray ionization-quadrupole-time-of-flight mass spectrometry (UPLC-PDA-ESI-Q-TOF-MS) and density functional theory (DFT) were used to explain the mechanism of structural transformation of C3G affecting their bioactivity at the molecular level. RESULTS: During the heating process at pH 2.2 to 7.0，the flavylium cation content of C3G decreased from 92.71% to 51.64% and the chalcone content increased from 7.29% to 30.61%. The quinoidal base and first discovery of the degradation product of the C3G, 1-(3,4-dihydroxy-phenyl)-2-(3, 4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-ethanone, were only detected in heated samples at pH 7.0. DFT revealed the antioxidant mechanism was mediated by sequential proton loss electron transfer and the antioxidant activity of C3G in pH 5.0 and 7.0 environments was higher than that in the pH 2.2 environment. CONCLUSIONS: The results revealed the thermal degradation products of C3G included catechin, 3,4-dihydroxybenzoic acid, 2,4,6-trihydroxy-benzaldehyde and 1-(3,4-Dihydroxy-phenyl)-2-(3,4,5-trihydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-ethanone. C3G had higher antioxidant activity in weakly acidic to near-neutral environments and the reactive sites were most likely at the 4'-OH and 5-OH sites. © 2021 Society of Chemical Industry.

User acceptance of smart home voice assistant: a comparison among younger, middle-aged, and older adults.

Voice assistants are widely used in smart home environments. This study aimed to investigate user acceptance of a smart home voice assistant. A questionnaire was designed, and 471 Chinese adults were recruited to complete the questionnaire. The data were analyzed using exploratory factor analysis and regression analysis. The results revealed that user requirements of adults were composed of six factors: hedonic motivation and trust (ß = .41, p < .001), social influence (ß = .22, p < .001), performance expectancy (ß = .15, p < .001), effort expectancy (ß = .08, p = .018), product features (ß = .15, p = .009), and facilitating conditions (ß = .06, p = .049). Among these six factors, hedonic motivation and trust are considered the most important. Younger, middle-aged, and older adults differed significantly in their requirements and acceptance of a smart home voice assistant. These findings have implications for the design of smart home voice assistants so that they are more acceptable to younger and older adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s10209-022-00936-1.

Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion.

To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Adult SD male rats were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 µL adenovirus in the right ventricle, then MCAO was performed for followed by reperfusion HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (all <0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (all <0.05), and ADP was decreased in the SIK2 overexpression group (all <0.05). SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.

L-tryptophan anaerobic fermentation for indole acetic acid production: Bacterial enrichment and effects of zero valent iron.

Indole acetic acid (IAA) as a plant hormone, was one of the valuable products of anaerobic fermentation. However, the enriching method remained unknown. Moreover, whether zero valent iron (ZVI) could enhance IAA production was unexplored. In this work, IAA producing bacteria Klebsiella (63 %) was enriched successfully. IAA average production rate and concentration were up to 3 mg/L/h and 56 mg/L. With addition of 1 g/L ZVI, IAA average production rate and concentration was increased for 2 and 3 folds. Mechanisms indicated ZVI increased Na+K+-ATP activity and electron transport activity for 2 folds and 1 fold. Moreover, macro transcription determined indole pyruvate pathway activity like primary-amine oxidase, indole pyruvate decarboxylase and aldehyde dehydrogenase were increased for 146 %, 187 %, and 557 %, respectively. Therefore, ZVI was suitable for enhancement IAA production from mixed culture anaerobic fermentation.

Enhancing docosahexaenoic acid production from Schizochytrium sp. by using waste Pichia pastoris as nitrogen source based on two-stage feeding control.

To reduce the cost of docosahexaenoic acid (DHA) production from Schizochytrium sp., the waste Pichia pastoris was successfully used as an alternative nitrogen source to achieve high-density cultivation during the cell growth phase. However, due to the high oxygen consumption feature when implementing high-density cultivation, the control of both the nitrogen source and dissolved oxygen concentration (DO) at each sufficient level was impossible; thus, two realistic control strategies, including "DO sufficiency-nitrogen limitation" and "DO limitation-nitrogen sufficiency", were proposed. When using the strategy of "DO sufficiency-nitrogen limitation", the lowest maintenance coefficient of glucose (12.3 mg/g/h vs. 17.0 mg/g/h) and the highest activities of related enzymes in DHA biosynthetic routes were simultaneously obtained; thus, a maximum DHA concentration of 12.8 ± 1.2 g/L was achieved, which was 1.58-fold greater than that of the control group. Overall, two-stage feeding control for alternative nitrogen sources is an efficient strategy to industrial DHA fermentation.

The enhancement effect of n-Fe3O4 on methyl orange reduction by nitrogen-fixing bacteria consortium.

Although the anaerobic reduction of azo dyes is ecofriendly, high ammonia consumption remains a significant challenge. This work enriched a mixed nitrogen-fixing bacteria consortium (NFBC) using n-Fe3O4 to promote the anaerobic reduction of methyl orange (MO) without exogenous nitrogen. The enriched NFBC was dominated by Klebsiella (80.77 %) and Clostridium (17.16 %), and achieved a 92.7 % reduction of MO with an initial concentration of 25 mg·L-1. Compared with the control, the consortium increased the reduction efficiency of MO, cytochrome c content, and electron transport system (ETS) activity by 11.86 %, 89.86 %, and 58.49 %, respectively. When using 2.5 g·L-1 n-Fe3O4, the extracellular polymeric substances (EPS) of NFBC were present in a concentration of 85.35 mg·g-1. The specific reduction rates of MO by NFBC were 2.26 and 3.30 times faster than those of Fe(II) and Fe(III), respectively, while the enrichment factor of the ribosome pathway in NFBC exceeded 0.75. Transcriptome, carbon consumption, and EPS analyses suggested that n-Fe3O4 stimulated carbon metabolism and secreted protein synthesized by the mixed culture. The latter occurred due to the increased activity of consortium and the content of redox substances. These findings demonstrate that n-Fe3O4 promoted the efficiency of mixed nitrogen-fixing bacteria for removing azo dyes from wastewater. This innovative approach highlights the potential of integrating nanomaterials with biological systems to effectively address complex pollution challenges.

Invasive cellular blue nevus in the cervical spine: A case report.

INTRODUCTION: Cellular blue nevus is an uncommon neoplasm in the spine. PATIENT CONCERNS: Here, we present a case of a 24 years old male with a 2 months history of numbness in the right upper limb and shoulder. DIAGNOSIS: Cervical spine and subcutaneous tissue invasive cellular blue nevus. INTERVENTIONS: The patient underwent C4 laminectomy and partial C3 and C5 laminectomy for total resection of the lesion. Histopathology revealed a nodular tumor with unclear boundaries, which was composed of heavily pigmented dendritic cells and more pigmented spindle cells. OUTCOMES: There was no recurrence during 3 years follow-up. CONCLUSION: Invasive cellular blue nevus of the spine can be wrongly diagnosed as spinal meningeal melanocytoma and meningeal melanoma due to its special cell behavior and rarity. Therefore, it is important to understand its pathological and clinical characteristics to avoid over-treatment.

MTHFD2-mediated redox homeostasis promotes gastric cancer progression under hypoxic conditions.

OBJECTIVES: Cancer cells undergo metabolic reprogramming to adapt to high oxidative stress, but little is known about how metabolic remodeling enables gastric cancer cells to survive stress associated with aberrant reactive oxygen species (ROS) production. Here, we aimed to identify the key metabolic enzymes that protect gastric cancer (GC) cells from oxidative stress. METHODS: ROS level was detected by DCFH-DA probes. Multiple cell biological studies were performed to identify the underlying mechanisms. Furthermore, cell-based xenograft and patient-derived xenograft (PDX) model were performed to evaluate the role of MTHFD2 in vivo. RESULTS: We found that overexpression of MTHFD2, but not MTHFD1, is associated with reduced overall and disease-free survival in gastric cancer. In addition, MTHFD2 knockdown reduces the cellular NADPH/NADP+ ratio, colony formation and mitochondrial function, increases cellular ROS and cleaved PARP levels and induces in cell death under hypoxia, a hallmark of solid cancers and a common inducer of oxidative stress. Moreover, genetic or pharmacological inhibition of MTHFD2 reduces tumor burden in both tumor cell lines and patient-derived xenograft-based models. DISCUSSION: our study highlights the crucial role of MTHFD2 in redox regulation and tumor progression, demonstrating the therapeutic potential of targeting MTHFD2.

Modified EBP-bFGF targeting endogenous renal extracellular matrix protects against renal ischemia-reperfusion injury in rats.

Acute kidney injury (AKI) is a life-threatening disease primarily caused by renal ischemia-reperfusion (I/R) injury, which can result in renal failure. Currently, growth factor therapy is considered a promising and effective approach for AKI treatment. Basic fibroblast growth factor (bFGF), an angiogenic factor with potent activity, efficiently stimulates angiogenesis and facilitates regeneration of renal tissue. However, the unrestricted diffusion of bFGF restricts its clinical application in AKI treatment. Therefore, developing a novel sustained released system for bFGF could enhance its potential in treating AKI. In this study, we genetically engineered a multifunctional recombinant protein by fusing bFGF with a specific peptide (EBP). EBP-bFGF effectively binds to the extracellular matrix in the injured kidney, enabling slow release of bFGF in AKI. Furthermore, following orthotopic injection into I/R rats' ischemic kidneys, EBP-bFGF exhibited stable retention within the tissue. Additionally, EBP-bFGF suppressed apoptosis of renal cells, reduced renal fibrosis, and facilitated recovery of renal function. These findings suggest that EBP-bFGF delivery system represents a promising strategy for treating AKI.

Controllable Preparation of a N-Doped Hierarchical Porous Carbon Framework Derived from ZIF-8 for Highly Efficient Capacitive Deionization.

Capacitive deionization (CDI) is a promising desalination technology, and metal-organic framework (MOF)-derived carbon as an electrode material has received more and more attention due to its designable structure. However, MOF-derived carbon materials with single-pore structures have been difficult to meet the technical needs of related fields. In this work, the ordered hierarchical porous carbon framework (OMCF) was prepared by the template method using zeolitic imidazolate frameworks-8 (ZIF-8) as a precursor. The pore structures, surface properties, electrochemical properties, and CDI performances of the OMCF were investigated and compared with the microporous carbon framework (MCF), also derived from ZIF-8. The results show that the hierarchical porous carbon OMCF possessed a higher specific surface area, better hydrophilic surface (with a contact angle of 13.45°), and higher specific capacitance and ion diffusion rate than those of the MCF, which made the OMCF exhibit excellent CDI performances. The adsorption capacity and salt adsorption rate of the OMCF in a 500 mg·L-1 NaCl solution at 1.2 V and a 20 mL·min-1 flow rate were 12.17 mg·g-1 and 3.34 mg·g-1·min-1, respectively, higher than those of the MCF. The deionization processes of the OMCF and MCF closely follow the pseudo-first-order kinetics, indicating the double-layer capacitance control. This work serves as a valuable reference for the CDI application of N-doped hierarchical porous carbon derived from MOFs.

Fabricating Ru Atom-Doped Novel FeP4/Fe2PO5 Heterogeneous Interface for Overall Water Splitting in Alkaline Environment.

Developing bifunctional electrocatalysts with low-content noble metals and high activity and stability is crucial for water splitting. Herein, we reported a novel Ru doped FeP4/Fe2PO5 heterogeneous interface catalyst (Ru@FeP4/Fe2PO5) for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) by heat treatment coupling electrodeposition strategy. Experiments disclosed that Ru@FeP4/Fe2PO5 proclaimed excellent catalytic activity for the OER (249 mV@100 mA cm-2) and HER (49 mV@10 mA cm-2) in a 1 M KOH environment. More importantly, the mass activity and turnover frequency of Ru@FeP4/Fe2PO5 were 117 and 108 times higher than that of commercial RuO2 at an overpotential of 300 mV during the OER, respectively. In addition, the assembled Ru@FeP4/Fe2PO5 || Ru@FeP4/Fe2PO5 system could retain superior durability in a two-electrode system for 134 h at 300 mA cm-2. Further mechanism studies revealed that Ru atoms in Ru@FeP4/Fe2PO5 act in a key role for the excellent activity during water splitting because the electronic structure of Ru sites could be optimized by the interaction between Ru and Fe atoms at the interface to strengthen the adsorption of reaction intermediates. Besides, the introduction of Ru atoms could also enhance the charge transfer, which effectually accelerates the reaction kinetics. The strategy of anchoring Ru atom on novel heterostructure provides a promising path to boost the overall activity of electrocatalysts for water splitting.

Investigating the Psychological, Social, Cultural, and Religious Predictors of COVID-19 Vaccine Uptake Intention in Digital Age: A Media Dependency Theory Perspective.

Media exposure to health communication contents related to the COVID-19 pandemic alone is inadequate to measure the influence of media on individuals in adopting precautionary behaviors against COVID-19, such as vaccine uptake. Certain individuals may pay attention to and be influenced by communication content. However, literature has suggested other instrumental determinants in developing and adopting health precautionary measures, such as culture or religion, especially regarding vaccination. In times of crisis, such as the COVID-19 pandemic, it is valuable to examine the interrelationships among psychological, sociocultural, and informational factors. This can provide valuable insights for policymakers in developing effective communication strategies. Drawing an analogy between the Media dependency theory (MDT) and the Theory of Planned Behavior (TPB) model, this study unravels the factors underpinning the COVID-19 vaccine uptake intention among Pakistanis. The study utilized a cross-sectional research design and employed a survey method to gather data from a sample of 993 participants. The findings obtained from the PLS-SEM analysis confirmed that individuals relied on both traditional and social media to cope with the COVID-19 pandemic. The findings show that individuals rely more on the informational content disseminated through conventional media channels. The findings also suggest that individuals from Asian countries, such as Pakistan, tend to be more inclined toward collectivism. The findings about the moderating role of religiosity suggest that religious beliefs significantly shape individuals' reliance on traditional media. Hence, this study has uniquely contributed to public health and media management by providing a strategy for managers to address disseminating misinformation related to religion and its impact on vaccination-related health issues. The study has theoretically confirmed the principles of media dependency theory. As a result, it is recommended that various information sources be utilized to cultivate resilience among individuals to manage health crises effectively.

Expression of codon-optimized PDCoV-RBD protein in baculovirus expression system and immunogenicity evaluation in mice.

Porcine deltacoronavirus (PDCoV) is a global epidemic enteropathogenic coronavirus that mainly infects piglets, and causes huge losses to the pig industry. However, there are still no commercial vaccines available for PDCoV prevention and controlment. Receptor-binding domain (RBD) is located at the S1 subunit of PDCoV and is the major target for developing viral inhibitor and vaccine. In this study, the characteristics of the RBD were analyzed by bioinformatic tools, and codon optimization was performed to efficiently express the PDCoV-RBD protein in the insect baculovirus expression system. The purified PDCoV-RBD protein was obtained and fully emulsified with CPG2395 adjuvant, aqueous adjuvant and Al(OH)3 adjuvant, respectively, to develop vaccines. The humoral and cellular immune responses were assessed on mice. The results showed that both the RBD/CPG2395 and RBD/aqueous adjuvant could induce stronger immune responses in mice than that of RBD/Al(OH)3. In addition, the PDCoV challenge infection was conducted and the RBD/CPG2395 could provide better protection against PDCoV in mice. Our study showed that the RBD protein has good antigenicity and can be used as a protective antigen, which provided a basis for the development of the PDCoV vaccine.

The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity.

In response to adverse environmental conditions, embryonic development may reversibly cease, a process termed diapause. Recent reports connect this phenomenon with the non-genetic responses of tumors to chemotherapy, but the mechanisms involved are poorly understood. Here, we establish a multifarious role for SMC4 in the switching of colorectal cancer cells to a diapause-like state. SMC4 attenuation promotes the expression of three investment phase glycolysis enzymes increasing lactate production while also suppressing PGAM1. Resultant high lactate levels increase ABC transporter expression via histone lactylation, rendering tumor cells insensitive to chemotherapy. SMC4 acts as co-activator of PGAM1 transcription, and the coordinate loss of SMC4 and PGAM1 affects F-actin assembly, inducing cytokinesis failure and polyploidy, thereby inhibiting cell proliferation. These insights into the mechanisms underlying non-genetic chemotherapy resistance may have significant implications for the field, advancing our understanding of aerobic glycolysis functions in tumor and potentially informing future therapeutic strategies.

Correction: Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates.

Correction for 'Catalytic (3 + 2) umpolung annulations of α-thioacyl carbenes with aryl isothiocyanates' by Ziyang Dong et al., Chem. Commun., 2022, 58, 7980-7983, https://doi.org/10.1039/D2CC02882D.