Rational Design of an Artificial Metalloenzyme by Constructing a Metal-Binding Site Close to the Heme Cofactor in Myoglobin.

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H2O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn2+ to Mn3+ using H2O2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.

[Response of branch attributes of Larix kaempferi to climate variables]. / 日本落叶松枝条属性特征对气候变量的响应.

We established a mixed-effects model incorporating climatic factors for the base diameter and length of the primary branches of Larix kaempferi using stepwise regression, based on climatic data from a total of 40 standard plots located in Xiaolongshan, Gansu Province, Changlinggang Forest Farm in Jianshi County, Hubei Province, and Dagujia Forest Farm in Qingyuan County, Liaoning Province, as well as the data from 120 L. kaempferi sample trees. Additionally, we created prediction charts for the fixed effects portion of the optimal mixed model to determine the relationship between climatic factors and base diameter and branch length, to explore the differential response of L. kaempferi branches to climatic variables. The results showed that the base diameter mixing model with annual mean temperature and water vapor deficit and the branch length mixing model with annual mean temperature had the best fitting effect, with R2 of 0.6152 and 0.6823, respectively. Based on the fixed effects prediction chart of the mixed model, the overall basal diameter showed an increasing trend with the increases of relative branch depth. The average basal diameter size was in an order of young-aged plantation

Five miRNAs identified in fucosylated extracellular vesicles as non-invasive diagnostic signatures for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent and aggressive cancer that presents significant challenges for early detection. This study introduces the GlyExo-Capture method for isolating fucosylated extracellular vesicles (Fu-EVs) from serum. We analyze microRNA (miRNA) profiles from Fu-EVs in 88 HCC patients and 179 non-HCC controls using next-generation sequencing (NGS) and identify five miRNAs (hsa-let-7a, hsa-miR-21, hsa-miR-125a, hsa-miR-200a, and hsa-miR-150) as biomarkers for HCC diagnosis. The five-miRNA panel demonstrates exceptional HCC diagnostic performance, with a sensitivity of 0.90 and specificity of 0.92 in a combined cohort of 194 HCC and 412 non-HCC controls, significantly surpassing the performance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP). Notably, the miRNA model achieves recall rates of 85.7% and 90.8% for stage 0 and stage A early-stage HCC, respectively, identifies 88.1% of AFP-negative HCC cases, and effectively differentiates HCC from other cancers. This study provides a high-throughput, rapid, and non-invasive approach for early HCC detection.

Post-translational modifications of pyruvate dehydrogenase complex in cardiovascular disease.

Pyruvate dehydrogenase complex (PDC) is a crucial enzyme that connects glycolysis and the tricarboxylic acid (TCA) cycle pathway. It plays an essential role in regulating glucose metabolism for energy production by catalyzing the oxidative decarboxylation of pyruvate to acetyl coenzyme A. Importantly, the activity of PDC is regulated through post-translational modifications (PTMs), phosphorylation, acetylation, and O-GlcNAcylation. These PTMs have significant effects on PDC activity under both physiological and pathophysiological conditions, making them potential targets for metabolism-related diseases. This review specifically focuses on the PTMs of PDC in cardiovascular diseases (CVDs) such as myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, obesity-related cardiomyopathy, heart failure (HF), and vascular diseases. The findings from this review offer theoretical references for the diagnosis, treatment, and prognosis of CVD.

FTO variant is associated with changes in BMI, ghrelin, and brain function following bariatric surgery.

BACKGROUNDA polymorphism in the fat mass and obesity-associated gene (FTO) is linked to enhanced neural sensitivity to food cues and attenuated ghrelin suppression. Risk allele carriers regain more weight than noncarriers after bariatric surgery. It remains unclear how FTO variation affects brain function and ghrelin following surgery.METHODSResting-state functional magnetic resonance imaging and cue-reactivity functional magnetic resonance imaging with high-/low-caloric food cues were performed before surgery and at 1, 6, and 12 months after surgery to examine brain function in 16 carriers with 1 copy of the rs9939609 A allele (AT) and 26 noncarriers (TT). Behavioral assessments up to 5 years after surgery were also conducted.RESULTSThe AT group relative to the TT group had smaller BMI loss at 12-60 months after surgery and lower resting-state activity in posterior cingulate cortex following laparoscopic sleeve gastrectomy (group-by-time interaction effects). Meanwhile, the AT group relative to the TT group showed greater food cue responses in dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and insula (group effects). There were negative associations of weight loss with ghrelin and greater activation in DLPFC, DMPFC and insula in the AT but not the TT group.CONCLUSIONThese findings indicate that FTO variation is associated with the evolution of ghrelin signaling and brain function after bariatric surgery, which might hinder weight loss.TRIAL REGISTRATIONChinese Clinical Trial Registry Center, ChiCTR-OOB-15006346.FUNDINGThis work was supported by the National Natural Science Foundation of China (grant nos. 82172023, 82202252, 82302292); National Key R&D Program of China (no. 2022YFC3500603); Natural Science Basic Research Program of Shaanxi (grant nos. 2022JC-44, 2022JQ-622, 2023-JC-QN-0922, 2023-ZDLSF-07); Fundamental Research Funds for the Central Universities (grant nos. ZYTS23188, XJSJ23190, XJS221201, QTZX23093); and the Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse (grant no. Y1AA3009).

Appropriate sulfur fertilization in contaminated soil enhanced the cadmium uptake by hyperaccumulator Sedum alfredii Hance.

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye.

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

SARS-CoV-2 spike-induced syncytia are senescent and contribute to exacerbated heart failure.

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Stress granules in atherosclerosis: Insights and therapeutic opportunities.

Atherosclerosis, a complex inflammatory and metabolic disorder, is the underlying cause of several life-threatening cardiovascular diseases. Stress granules (SG) are biomolecular condensates composed of proteins and mRNA that form in response to stress. Recent studies suggest a potential link between SG and atherosclerosis development. However, there remain gaps in understanding SG role in atherosclerosis development. Here we provide a thorough analysis of the role of SG in atherosclerosis, covering cellular stresses stimulation, core components, and regulatory genes in SG formation. Furthermore, we explore atherosclerosis induced factors such as inflammation, low or oscillatory shear stress (OSS), and oxidative stress (OS) may impact SG formation and then the development of atherosclerotic lesions. We have assessed how changes in SG dynamics impact pro-atherogenic processes like endothelial dysfunction, lipid metabolism, and immune cell recruitment in atherosclerosis. In summary, this review emphasizes the complex interplay between SG and atherosclerosis that could open innovative directions for targeted therapeutic strategies in preventing or treating atherosclerotic cardiovascular diseases.

Prevalence and risk factors of deep venous thrombosis of hospitalizations in plateau: a cross-section analysis.

BACKGROUND: Deep venous thrombosis (DVT) is a serious public health issue that threatens human health and economic development. Presently, differences in the prevalence of DVT among individuals from different nationalities, residents of high-altitude areas, and those consuming any special diet are unknown. Therefore, we aimed to elucidate the prevalence of and the associated risk factors for DVT in hospitalized patients in the plateau areas. METHODS: The subjects were hospitalized patients in three grade III-a hospitals in the Qinghai Province, China, during January-October 2020. The demographic, clinical, and laboratory data were collected at admission, and ultrasonography of the bilateral lower extremities was performed. The hospital stay-duration was recorded at the time of discharge. RESULTS: A total of 3432 patients were enrolled, of which 159 (4.60%) were diagnosed with DVT. The age of > 50 years (OR = 2.434, 95% CI: 1.521-3.894252, P < 0.001), residence altitude of ≥ 3000 m (OR = 2.346, 95% CI: 1.239-4.440, P = 0.009), D-dimer level of ≥ 0.5 mg/L (OR = 2.211, 95% CI: 1.547-3.161, P < 0.001), presence of comorbidities (OR = 1.904, 95% CI: 1.386-2.705, P < 0.001), a history of varicose veins (OR = 1.990, 95% CI: 0.959-4.128, P = 0.045), and current medications (OR = 2.484, 95% CI: 1.778-3.471, P < 0.001) were identified as risk factors for DVT in these plateau areas. CONCLUSION: The prevalence of DVT in the hospitalized patients of the studied plateau areas was 4.60%. We recommend considering individualized risk stratification (age > 50 years, residence altitude ≥ 3000 m, a history of varicose veins, D-dimer level ≥ 0.5 mg/L, current medications, and comorbidities) for patients at the time of admission.

Electron Tandem Transport Channel in a Cu3P/Sv-ZnIn2S4 p-n Heterojunction for Photothermal-Photocatalytic Benzyl Alcohol Oxidation and H2 Production.

The development of photocatalytic systems with an electron tandem transport channel represents a promising avenue for improving the utilization of photogenerated electrons and holes despite encountering significant challenges. In this study, ZnIn2S4 (Sv-ZIS) with sulfur vacancies was fabricated using a solvothermal technique to create defect energy levels. Subsequently, Cu3P nanoparticles were coupled onto the surface of Sv-ZIS, forming a Cu3P/Sv-ZIS p-n heterojunction with an electron tandem transport channel. Experimental findings demonstrated that this tandem transport channel enhanced the carrier lifetime and separation efficiency. In addition, mechanistic investigations unveiled the formation of a robust built-in electric field (BEF) at the interface between Cu3P and Sv-ZIS, providing a driving force for electron migration. The combined consequences of the transport channel, the strong BEF, and photothermal effect led to a surface carrier separation efficiency of 65.85%. Consequently, Cu3P/Sv-ZIS achieved simultaneous H2 yield and benzaldehyde production rates of 18,101.4 and 15,012.6 µmol·g-1·h-1, which were 2.31 and 2.62 times higher than those of ZnIn2S4, respectively. This work exemplifies the design of the p-n heterojunction for the efficient utilization of photogenerated electrons and holes.

Investigation of the genetic and clinical features of laterality disorders in prenatal diagnosis: discovery of a novel compound heterozygous mutation in the DNAH11 gene.

BACKGROUND: Left-right laterality disorders are a heterogeneous group of disorders caused by an altered position or orientation of the thoracic and intra-abdominal organs and vasculature across the left-right axis. They mainly include situs inversus and heterotaxy. Those disorders are complicated by cardiovascular abnormalities significantly more frequently than situs solitus. METHODS: In this study, 16 patients with a fetal diagnosis of laterality disorder with congenital heart defects (CHD) were evaluated with a single nucleotide polymorphism array (SNP-arry) combined with whole-exome sequencing (WES). RESULTS: Although the diagnostic rate of copy number variations was 0 and the diagnostic rate of WES was 6.3% (1/16), the likely pathogenic gene DNAH11 and the candidate gene OFD1 were ultimately identified. In addition, novel compound heterozygous mutations in the DNAH11 gene and novel hemizygous variants in the OFD1 gene were found. Among the combined CHD, a single atrium/single ventricle had the highest incidence (50%, 8/16), followed by atrioventricular septal defects (37.5%, 6/16). Notably, two rare cases of common pulmonary vein atresia (CPVA) were also found on autopsy. CONCLUSION: This study identified the types of CHD with a high incidence in patients with laterality disorders. It is clear that WES is an effective tool for diagnosing laterality disorders and can play an important role in future research.

Prenatal diagnosis of a severe form of frontonasal dysplasia with severe limb anomalies, hydrocephaly, a hypoplastic corpus callosum, and a ventricular septal defect using 3D ultrasound: a case report and literature review.

BACKGROUND: Frontonasal dysplasia (FND) is a rare congenital anomaly resulting from the underdevelopment of the frontonasal process, and it can be syndromic or nonsyndromic. The typical features of FND include a deformed nose and ocular hypertelorism, which are sometimes associated with cleft lip and/or palate. Only approximately 10 cases of prenatally diagnosed nonsyndromic FND have been reported in the past 30 years. CASE PRESENTATION: A 33-year-old woman (G2P1) was referred to our center at 20 gestational weeks for bilateral hydrocephaly. We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using three-dimensional (3D) ultrasound. A hypoplastic corpus callosum, unilateral microtia, and a ventricular septal defect were also detected. Genetic testing, including karyotype analysis, copy number variation (CNV) analysis, trio-whole exome sequencing (trio-WES), and trio-whole-gene sequencing (trio-WGS), was performed; however, we did not find any de novo gene variants in the fetus as compared to the parents. Postmortem examination confirmed the prenatal diagnosis of FND. CONCLUSION: The present case expands the wide phenotypic spectrum of prenatal FND patients. 3D ultrasound is a useful tool for detecting facial and limb deformities.

Evaluation of Carotid Stiffness in Metabolic Syndrome by Real-Time Shear Wave Elasticity Imaging and Ultrafast Pulse Wave Velocity.

OBJECTIVE: This study utilized real-time shear wave elasticity imaging (SWE) and ultrafast pulse wave velocity (ufPWV) to assess carotid arterial stiffness, aiming to predict atherosclerosis risk in patients with metabolic syndrome (MS). METHODS: In this study, 181 patients with metabolic syndrome (MS group) were compared with 73 healthy adults. The MS group was divided into three groups: MS I group: CIMT was normal (CIMT < 1.0 mm, no plaque, n = 61); MS II group: CIMT thickening (1.0 mm ≤ CIMT<1.5 mm, no plaque, n = 39); MS III group: plaque group (CIMT ≥ 1.5 mm, plaque, n = 81). Concurrently, the group of 73 healthy individuals was designated as the control set (NC). Parameters assessed include carotid intima-media thickness (CIMT), elastic modulus values of the carotid artery's anterior and posterior walls (Mean, Max, Min), pulse wave velocity at systole's commencement (PWV-BS), and pulse wave velocity at systole's termination (PWV-ES). Differences, distribution characteristics, and correlations across these groups were analyzed. RESULTS: A significant association was found between PWV-BS, PWV-ES, and arteriosclerosis severity, with these factors gaining importance as arteriosclerosis progressed. Notably, PWV-ES differences were significant across the four groups (p < 0.05). Both MS III and MS II groups exhibited higher PWV-ES values compared to the MS I group and controls. Statistically significant differences were observed between MS III, MS II, and MS I groups relative to the control group (p < 0.05). Additionally, the Mean, Max, and Min values of the anterior and posterior carotid walls in the MS III group surpassed those of the other groups. CONCLUSION: Real-time shear wave elasticity imaging and ultrafast pulse wave velocity are valuable tools for assessing atherosclerosis risk in MS patients. These non-invasive, safe, and reproducible imaging techniques can quantitatively evaluate the stiffness of the common carotid artery's wall, offering important insights into cardiovascular risk assessment.

Mixture composition design of magnesium oxychloride cement-stabilized crushed stone materials applied as a pavement base.

Conventional binding materials, such as silicate cement and lime, present high energy consumption, pollution, and carbon emissions. Therefore, we utilize crushed stone as a stabilization material. Magnesium oxychloride cement (MOC) is modified and used as an inorganic admixture owing to its eco-friendly nature and low carbon content. We analysed the control indicators of an integrated design of MOC-stabilized crushed stone by conducting unconfined compressive strength and water-resistance tests. The optimum mixing composition of the MOC-stabilized crushed stone was determined through the response surface methodology. We determined the best approach and dosage for improving the water resistance of MOC-stabilized crushed stone by comparing the effects of four modification methods: fly ash, citric acid + silica fume, phosphoric acid + waterborne polyurethane, and dihydrogen phosphate potassium salt. We also perform a comparison with 5% ordinary silicate cement-stabilized crushed stone. The results indicate that the MOC-stabilized crushed stone exhibits a rapid increase in strength in the early stage, but this rate reduces after 28 days. The mixing design employs the 4-day unconfined compressive strength and 1-day water resistance coefficient as the technical indicators. The best mixing composition includes a 4.27% MOC dosage and a molar ratio of MgO/MgCl2 of 5.85. We use 1% citric acid + 10% silica fume in equal amounts to replace the MOC dopant method for composite modification of the MOC stabilized crushed stone. Consequently, the 1-day water resistance coefficient before water immersion is significantly increased from 0.78 to 0.91 and its 4-day unconfined compressive strength is only reduced by 0.10 MPa. This significantly improves the water resistance of the MOC-stabilized crushed stone and ensures that its strength remains unaffected, which is the optimal modification method. However, this method must ensure that a small amount of citric acid and silica fume are uniformly distributed in the MOC-stabilized crushed stone, which increases the construction difficulty of the road base.

Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential.

Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.

Evaluating the protective capacity of soil heavy metals regulation limits on human health: A critical analysis concerning risk assessment - Importance of localization.

Heavy metal pollution of agricultural soil is a major global concern, prompting the establishment of maximum allowable limits (MALs) to ensure food safety and protect human health. This study collected and compared MALs for six heavy metals (As, Cd, Hg, Pb, Zn, and Cu) in agricultural soils from representative countries and organizations (EU and WHO/FAO). The research evaluated the critical health risks and efficacy of these MALs under the hypothetical scenario of metals concentrations reaching the maximum allowable level. Safe thresholds for heavy metals were then derived based on maximum acceptable health risk levels. The comparative analysis revealed significant variations in the specific limit values and terms of MALs across countries and organizations, even for the same metal. This suggests that there is no consensus among countries and organizations regarding the level of metal-related health risks. Furthermore, the risk analysis of metal concentrations reaching the maximum level accentuated heightened risks associated with As, suggesting that the current risk of soil As exposure was underestimated, particularly for children. However, soil Cu, Cd, and Zn limits generally resulted in low health risks, implying that the current limits may overestimate their hazard. Overall, the results highlight that the current MALs for soil heavy metals may not fully safeguard human health. There is a critical need to optimize current soil MALs based on localized risks and the actual impact of these metals on human health. It is suggested to appropriately lower the limits of metals (such as As) whose impact on health risks is underestimated, and cautiously increase the limits of metals (such as Cu, Cd, and Zn) that currently pose minor health risks. This approach aims to reduce both over and insufficient protection problems of soil heavy metal MALs, emphasizing the importance of considering the locality in setting these limits.

A Long Photoperiod Promoted the Development, Reproduction, and Predation of Harmonia axyridis Pallas (Coleoptera: Coccinellidae) at an Average Greenhouse Temperature during the Winter.

To explore the feasibility of adjusting the photoperiod to regulate the life parameters and predation ability of Harmonia axyridis Pallas in greenhouses during the winter, life tables were constructed for H. axyridis under the three following photoperiods: 9L:15D (light/dark), 12L:12D, and 16L:8D at 15 °C, an average greenhouse temperature during the winter when aphids severely damage vegetables. The effects of photoperiods on predation by this ladybird were tested in both laboratory and greenhouse settings. The results showed that increased illumination promoted the development and reproduction of H. axyridis; under medium and long photoperiods, the pre-adult periods were 3.61 days and 4.34 days shorter than that under the short photoperiod, respectively, and the fecundity increased by 1.78 and 2.41 times. Population parameters r, λ, and R0 increased as illumination time increased, whereas T decreased. Increased illumination also increased the predation by third- and fourth-instar larvae and adults. The amounts of predation by fourth-instar larvae and adults increased by 22.16% and 75.09% under the medium photoperiod, and those under the long photoperiod increased by 71.96% and 89.64%, respectively. The numbers of Myzus persicae Sulzer predated by H. axyridis under the long photoperiod were higher than those under the short photoperiod in a greenhouse, and the predation parameters were influenced.

Assessing and Comparing Potential Allergenicity of Two Partially Hydrolyzed Whey-Based Formulas for Infants: A Population-Based Study in China.

SCOPE: In cases where breast milk is unavailable or inadequate, hydrolyzed infant formula is recommended as the primary alternative. The aim of this study is to assess and compare the allergenicity of two partially hydrolyzed whey-based formulas (PHF-Ws) using serum samples from patients with cow's milk allergy (CMA). METHODS AND RESULTS: LC-MS/MS technology is used to investigate the peptide distribution in both samples. The immunoreactivity of two PHF-Ws in 27 serum samples from 50 Chinese infants (02 years) with CMA is analyzed. The results demonstrate that even with a similar a degree of hydrolysis (DH), primary protein sources, peptides with molecular weights <5 kDa, and differences in the number of residual allergenic epitopes in the hydrolyzed peptide segments can lead to varying immune responses. CONCLUSION: The two PHF-Ws have notably high intolerance rates, exceeding 10% among infants with CMA. Therefore, suggesting that PHF-Ws may not be suitable for infants and children with CMA in China.

Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.