Search

Abstract Background Mindfulness-based stress reduction (MBSR) intervention has been widely used to reduce the burden of symptoms in cancer patients, and its effectiveness has been proven. However, the effectiveness of MBSR on depression, anxiety, fatigue, quality of life (QOL), posttraumatic growth (PTG), fear of cancer recurrence (FCR), pain, and sleep in breast cancer patients has not yet been determined. This study aims to determine the role of mindfulness-based stress reduction therapy in patients with breast cancer. Objectives The objective was to systematically review the literature to explore the effect of MBSR on anxiety, depression, QOL, PTG, fatigue, FCR, pain, stress and sleep in breast cancer patients. To explore the effect of 8-week versus 6-week MBSR on the 9 indicators. Data were extracted from the original RCT study at the end of the intervention and three months after baseline to explore whether the effects of the intervention were sustained. Methods We conducted searches on PubMed, Web of Science, Embase, and China National Knowledge Infrastructure from inception to November 2023. Eligible studies included randomized controlled trials of breast cancer patients who received mindfulness stress reduction intervention, reporting outcomes for anxiety, depression, fatigue, QOL, PTG, FCR, pain, stress, and sleep. Two researchers conducted separate reviews of the abstract and full text, extracted data, and independently evaluated the risk of bias using the Cochrane ‘Bias Risk Assessment tool’. The meta-analysis utilized Review Manager 5.4 to conduct the study, and the effect size was determined using the standardized mean difference and its corresponding 95% confidence interval. Results The final analysis included 15 studies with a total of 1937 patients. At the end of the intervention, the interventions with a duration of eight weeks led to a significant reduction in anxiety [SMD=-0.60, 95% CI (-0.78, -0.43), P

Abstract Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

AIM: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. METHODS: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. RESULTS: For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P

Abstract The engineered TadA variants used in cytosine base editors (CBEs) present distinctive advantages, including a smaller size and fewer off-target effects compared to cytosine base editors that rely on natural deaminases. However, the current TadA variants demonstrate a preference for base editing in DNA with specific motif sequences and possess dual deaminase activity, acting on both cytosine and adenosine in adjacent positions, limiting their application scope. To address these issues, we employ TadA orthologs screening and multi sequence alignment (MSA)-guided protein engineering techniques to create a highly effective cytosine base editor (aTdCBE) without motif and adenosine deaminase activity limitations. Notably, the delivery of aTdCBE to a humanized mouse model of Duchenne muscular dystrophy (DMD) mice achieves robust exon 55 skipping and restoration of dystrophin expression. Our advancement in engineering TadA ortholog for cytosine editing enriches the base editing toolkits for gene-editing therapy and other potential applications.

Abstract Organic crystal-based superimposed heterostructures with inherent multichannel characteristics demonstrate superior potential for manipulating excitons/photons at the micro/nanoscale for integrated optoelectronics. However, the precise construction of organic superimposed heterostructures with fixed superimposed sites remains challenging because of the random molecular nucleation process. Here, organic vertically superimposed heterostructures (OSHs) with fixed superimposed positions are constructed via semi-wrapped core/shell heterostructures with partially exposed cores, which provide preferential nucleation sites for further molecular epitaxial growth processes. Furthermore, the relative length ratio from 21.7% to 95.3% between interlayers is accurately adjusted by regulating the exposed area of the semi-wrapped core/shell heterostructures. Significantly, these OSHs with anisotropic optical characteristics demonstrate well regulation of excitation position-dependent waveguide behaviors and can function as photonic barcodes for information encryption. This strategy provides a facile approach for controlling the nucleation sites for the controllable preparation of organic heterostructures and advanced applications for integrated optoelectronics.

Abstract Expression profiling in spatially defined regions is crucial for systematically understanding tissue complexity. Here, we report a method of photo-irradiation for in-situ barcoding hybridization and ligation sequencing, named PBHL-seq, which allows targeted expression profiling from the photo-irradiated region of interest in intact fresh frozen and formalin fixation and paraffin embedding (FFPE) tissue samples. PBHL-seq uses photo-caged oligodeoxynucleotides for in situ reverse transcription followed by spatially targeted barcoding of cDNAs to create spatially indexed transcriptomes of photo-illuminated regions. We recover thousands of differentially enriched transcripts from different regions by applying PBHL-seq to OCT-embedded tissue (E14.5 mouse embryo and mouse brain) and FFPE mouse embryo (E15.5). We also apply PBHL-seq to the subcellular microstructures (cytoplasm and nucleus, respectively) and detect thousands of differential expression genes. Thus, PBHL-seq provides an accessible workflow for expression profiles from the region of interest in frozen and FFPE tissue at subcellular resolution with areas expandable to centimeter scale, while preserving the sample intact for downstream analysis to promote the development of transcriptomics.

Abstract Background The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). Methods and results In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. Conclusions Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC. Graphical abstract

Abstract Using renewable electricity to convert CO2 into CO offers a sustainable route to produce a versatile intermediate to synthesize various chemicals and fuels. For economic CO2-to-CO conversion at scale, however, there exists a trade-off between selectivity and activity, necessitating the delicate design of efficient catalysts to hit the sweet spot. We demonstrate here that copper co-alloyed with isolated antimony and palladium atoms can efficiently activate and convert CO2 molecules into CO. This trimetallic single-atom alloy catalyst (Cu92Sb5Pd3) achieves an outstanding CO selectivity of 100% (±1.5%) at −402 mA cm−2 and a high activity up to −1 A cm−2 in a neutral electrolyte, surpassing numerous state-of-the-art noble metal catalysts. Moreover, it exhibits long-term stability over 528 h at −100 mA cm−2 with an FECO above 95%. Operando spectroscopy and theoretical simulation provide explicit evidence for the charge redistribution between Sb/Pd additions and Cu base, demonstrating that Sb and Pd single atoms synergistically shift the electronic structure of Cu for CO production and suppress hydrogen evolution. Additionally, the collaborative interactions enhance the overall stability of the catalyst. These results showcase that Sb/Pd-doped Cu can steadily carry out efficient CO2 electrolysis under mild conditions, challenging the monopoly of noble metals in large-scale CO2-to-CO conversion.

The extrinsic black tooth stain (EBS) is commonly found in primary dentition. Patients cannot clean the EBS; this can only be done by professional scaling and debridement. It also has a tendency to reform, which significantly compromises children's aesthetics and even affects their quality of life. However, there is no conclusive evidence on the etiology of the EBS. The associations between the EBS and related oral microbial features is one of the research hot topics. No literature review summarized these research progresses in this area. Therefore, we reviewed the literature on the microbiology of the EBS since 1931 and reported as the following 5 aspects: molecular biotechnology, morphological structure and physiochemical characteristics, microbial etiology hypothesis and core microbial characteristics. The EBS is a special dental plaque mainly composed of Gram-positive bacilli and cocci with scattered calcium deposits that acquired salivary pellicle activates. Early studies showed that the Actinomyces was the main pathogenic bacteria. With advances in biological research techniques, the ‘core microbiome’ was proposed. The potential pathogenic genera were Actinomyces, Prevotella nigrescens, Pseudotropinibacterium, Leptotrichia, Neisseria and Rothia. However, the pathogenic species of the above genera were still unclear. Currently, it is believed that the EBS consists of iron compounds or black substances that oral bacterial metabolism produces or that the bacterial metabolites formed after chemical reactions in the micro-ecological environment.

The objective of the study was to investigate the effect of radio frequency parameters on the thawing time and the uniformity. During the radio frequency thawing of frozen chicken breast at 27.12 MHz and 6 kW, the effects of operating parameters such as electrode gap (8, 9, 10, and 11 cm), voltage (70%, 75%, and 80%) and sample thickness (4, 5, and 6 cm) on the pattern of temperature rise and the uniformity were examined. The results showed that with decreasing electrode gap and increasing voltage and sample thickness, the temperature rise accelerated and the uniformity index decreased. The optimum parameters were determined as 9 cm and 75% for electrode gap and voltage, respectively based on the thawing time and temperature distribution. Compared with thawing at ambient temperature (20 ℃, 6 h), the thawing time with radio frequency was shortened to 54.67 min, and the total viable count, the drip loss and total volatile basic nitrogen (T-VBN) content were significantly reduced (P < 0.05). The results of this study provide a theoretical basis and technical support for the practical application of radio frequency technology in the field of meat thawing.

Abstract Background The parallel evolution of similar traits or species provides strong evidence for the role of natural selection in evolution. Traits or species that evolved repeatedly can be driven by separate de novo mutations or interspecific gene flow. Although parallel evolution has been reported in many studies, documented cases of parallel evolution caused by gene flow are scarce by comparison. Aquilegia ecalcarata and A. kansuensis belong to the genus of Aquilegia, and are the closest related sister species. Mutiple origins of A. ecalcarata have been reported in previous studies, but whether they have been driven by separate de novo mutations or gene flow remains unclear. Results In this study, We conducted genomic analysis from 158 individuals of two repeatedly evolving pairs of A. ecalcarata and A. kansuensis. All samples were divided into two distinct clades with obvious geographical distribution based on phylogeny and population structure. Demographic modeling revealed that the origin of the A. ecalcarata in the Eastern of China was caused by gene flow, and the Eastern A. ecalcarata occurred following introgression from Western A. ecalcarata population. Analysis of Treemix and D-statistic also revealed that a strong signal of gene flow was detected from Western A. ecalcarata to Eastern A. ecalcarata. Genetic divergence and selective sweep analyses inferred parallel regions of genomic divergence and identified many candidate genes associated with ecologically adaptive divergence between species pair. Comparative analysis of parallel diverged regions and gene introgression confirms that gene flow contributed to the parallel evolution of A. ecalcarata. Conclusions Our results further confirmed the multiple origins of A. ecalcarata and highlighted the roles of gene flow. These findings provide new evidence for parallel origin after hybridization as well as insights into the ecological adaptation mechanisms underlying the parallel origins of species.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Objective: Whether to continue administering immunotherapy to patients with advanced non-small cell lung cancer (NSCLC) who have experienced tumor progression remains controversial after immunotherapy. The aims were to explore survival outcomes after further immunotherapy post-progression and to determine the optimal combination therapy in such cases. Methods: Overall, 507 patients with NSCLC who underwent immunotherapy and experienced tumor progression were retrospectively divided into Immuno-combination and No-immuno groups according to whether additional combination therapy involving immunotherapy was administered post-progression. Progression-free survival (PFS) and overall survival (OS) were evaluated. Subgroup analyses were performed according to the different treatment regimens for patients in the Immuno-combination group. Results: After propensity score matching, there were 150 patients in the No-immuno group and 300 patients in the Immuno combination group. Superior PFS was observed in the Immuno-combination group compared with those in the No-immuno group (6-month PFS: 25.3 % vs. 60.6 %; 12-month PFS: 6.7 % vs. 24.4 %; P < 0.001). Similar intergroup differences were observed for OS (12-month OS: 22.3 % vs. 69.4 %; 18-month OS: 6.4 % vs. 40.4 %; P < 0.001). Superior PFS outcomes were observed in the Immuno+Antiangiogenic group compared with the Immuno+Chemo group (6-month PFS: 51.3 % vs. 71.5 %; 12-month PFS: 23.1 % vs. 25.7 %; P = 0.017). Similar differences in OS were observed between those same subgroups (12-month OS: 62.1 % vs. 77.9 %; 18-month OS: 33.3 % vs. 48.7 %; P = 0.006). Conclusion: Patients with NSCLC experiencing tumor progression post-immunotherapy can still benefit from further treatment, with immunotherapy combined with antiangiogenic therapy the most efficacious option.

Objective: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. Methods: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection (BTI) following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. Results: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 BTI, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 BTI following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 BTI after primary vaccination. Conclusions: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.

Total knee arthroplasty (TKA) is an effective treatment for end-stage knee joint diseases. The debate over preserving or sacrificing the posterior cruciate ligament (PCL) in mobile-bearing TKA (MB TKA) still needs to be solved due to the lack of high-quality evidence, particularly meta-analyses comparing these techniques. This study aims to conduct a meta-analysis to compare the outcomes of PCL retention (CR) and PCL sacrifice (PS) in terms of clinical and functional knee scores, range of motion, complication rates, and revision rates and to validate these findings through animal experiments. A comprehensive search was conducted using MEDLINE, Cochrane, and Embase databases. Relevant studies were selected for the meta-analysis using RevMan 5.3. Additionally, an animal experiment using Sprague-Dawley rats simulated MB TKA to compare the effects of PCL retention and sacrifice surgeries. 12 studies were included in the meta-analysis. No significant differences were found between CR and PS techniques regarding HSS, KSS, KSFS, WOMAC, ROM, and medial/lateral instability. However, CR MB showed slight superiority in NKJS, while PS MB had better outcomes in complication and revision rates. In the animal study, CR rats exhibited significant early postoperative inflammation, but both groups’ knee structures gradually normalized. The meta-analysis indicates that PCL retention (CR MB) and sacrifice (PS MB) have similar effects on various clinical and functional knee scores. However, PS MB is significantly better at reducing complications and revision rates. The animal experiment confirms PS MB’s advantages in reducing inflammation and promoting joint recovery. Despite the strong evidence, long-term follow-up and larger-scale randomized controlled trials are necessary to confirm these findings.

BackgroundOrnithine transcarbamylase deficiency (OTCD), a rare hereditary disease caused by gene mutation of ornithine transcarbamylase (OTC), is the most prevalent type among urea cycle disorders. OTCD typically leads to mitochondrial enzyme dysfunction, preventing the synthesis of citrulline from carbamoyl phosphate and ornithine, and is characterized by a remarkable increase in blood ammonia. Specific symptoms may include neurological abnormalities, growth retardation, and other manifestations.MethodsWe presented a case of a child diagnosed with OTCD (OMIM: 311250). By using whole-genome sequencing (WGS) for the pedigree and in-depth whole-exome sequencing (WES), we aimed to identify the disease-causing genes. Gene mutation prediction tools were employed to verify the pathogenicity, and the molecular dynamics simulation method was utilized to assess the impact of this mutation on the activity and structural stability of the OTC protein.ResultsWhole-exome sequencing detected an OTC variant [NM_000531: c.622 (exon6) G > A, p.A208T]. Through comprehensive analysis with various gene mutation prediction tools and in line with the ACMG guidelines, this mutation site was firmly established as a pathogenic site. Moreover, the molecular dynamics simulation results clearly demonstrated that this mutation would significantly compromise the stability of the OTC protein structure.ConclusionThis study deepens our understanding of the clinical manifestations and characteristics of OTCD, especially the OTC A208T gene mutation site. Given the lack of specific clinical manifestations in OTCD patients, early and accurate diagnosis is crucial for effective treatment and prognosis improvement. To our knowledge, this is the first case of this mutation site reported in China.

Serological detection of hepatitis B virus markers plays a vital role in the diagnosis, treatment, prognosis, and therapeutic surveillance of hepatitis B. To compare the diagnostic performance of Autolumo A2000Plus and Abbott Architect i2000 systems in the detection of hepatitis B infection markers. A total of 6 HBV seroconversion panels and 743 participants were enrolled in this study, including 383 HBV-infected patients and 360 healthy adults. Clinical diagnostic information, laboratory results, and HBV genotyping were collected to evaluate the diagnostic performance of the A2000Plus and i2000 systems in detecting HBV infection markers. The results showed that the total percent agreement of HBV markers was all >90 % in both detection systems among the six seroconversion panels and 743 serum samples from the population. The χ2 values of the Chi-square test among hepatitis B virus serological markers in both analyzers were between 550.7 and 743.0, p

Abstract Background In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. Methods A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case–control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. Results A significant decrease in ANB (P

Abstract The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

The effect of legume proteins (soy protein (SP), chickpea protein (CP) and peanut protein (PP)) on the properties of wheat starch-lauric acid (WS-LA) system and its intrinsic mechanism were investigated. RVA, digestion experiment and TGA results showed that legume proteins prompted the viscosity peak formation during cooling stage and increased anti-digestion and thermal stability of WS-LA system. FT-IR, Raman, XRD and 13C NMR results indicated that legume proteins improved the long-range and short-range ordering degree and single-helix structure of WS-LA system. SP had greater influence on the properties of WS-LA system than that of CP and PP. Proteins with high solubility, emulsifying properties and β-sheet content were conducive to starch-based complexes formation. Molecular dynamics simulation results indicated that major forces for WS-LA-SP formation were hydrogen bonding and van der Waals forces. This study offered crucial information on starch-fatty acid-protein complexes formation for proteins selection in starch-based products development.

Acute intermittent porphyria (AIP) is caused by mutations in the gene encoding hydroxymethylbilane synthase (HMBS), a key enzyme in the heme biosynthesis pathway. AIP is an autosomal dominant disorder characterized by low penetrance and a highly heterogenous clinical presentation. The estimated prevalence of AIP is 5–10 cases per 100,000 persons, with acute attacks manifesting in less than 1% of the at-risk population. This low frequency of attacks suggests significant roles for oligogenic inheritance and environmental factors in the pathogenesis of the disease. In recent years, identification of several modifier genes has advanced our understanding of the factors influencing AIP penetrance and disease severity. This review summarizes these factors including the impact of specific HMBS mutations, oligogenic inheritance, mitochondrial DNA copy number, age, sex, the influence of sex hormones, and the role of environmental factors. Further studies into the etiology of AIP disease penetrance should inform pathogenesis, potentially allowing for the development of more precise diagnostic and therapeutic approaches.

Summary: The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and

Microbially induced carbonate precipitation (MICP), as an eco-friendly and promising technology that can transform free metal ions into stable precipitation, has been extensively used in remediation of heavy metal contamination. However, its depressed efficiency of heavy metal elimination remains in question due to the inhibition effect of heavy metal toxicity on bacterial activity. In this work, an efficient, low-cost manganese (Mn) elimination strategy by coupling MICP with chitosan biopolymer as an additive with reduced treatment time was suggested, optimized, and implemented. The influences of chitosan at different concentrations (0.01, 0.05, 0.10, 0.15 and 0.30 %, w/v) on bacterial growth, enzyme activity, Mn removal efficiency and microstructure properties of the resulting precipitation were investigated. Results showed that Mn content was reduced by 94.5 % within 12 h with 0.15 % chitosan addition through adsorption and biomineralization as MnCO3 (at an initial Mn concentration of 3 mM), demonstrating a two-thirds decrease in remediation time compared to the chitosan-absent system, whereas maximum urease activity increased by ∼50 %. Microstructure analyses indicated that the mineralized precipitates were spherical-shaped MnCO3, and a smaller size and more uniform distribution of MnCO3 is obtained by the regulation of abundant amino and hydroxyl groups in chitosan. These results demonstrate that chitosan accelerates nucleation and tunes the growth of MnCO3 by providing nucleation sites for mineral formation and alleviating the toxicity of metal ions, which has the potential to upgrade MICP process in a sustainable and effective manner. This work provides a reference for further understanding of the biomineralization regulation mechanism, and gives a new perspective into the application of biopolymer-intensified strategies of MICP technology in heavy metal contamination.