Exposure to microplastics renders immunity of the thick-shell mussel more vulnerable to diarrhetic shellfish toxin-producing harmful algae.

Despite both microplastics (MPs) and harmful algae blooms (HABs) may pose a severe threat to the immunity of marine bivalves, the toxification mechanism underlying is far from being fully understood. In addition, owing to the prevalence and sudden occurrence characteristics of MPs and HABs, respectively, bivalves with MP-exposure experience may face acute challenge of harmful algae under realistic scenarios. However, little is known about the impacts and underlying mechanisms of MP-exposure experience on the susceptibility of immunity to HABs in bivalve mollusks. Taking polystyrene MPs and diarrhetic shellfish toxin-producing Prorocentrum lima as representatives, the impacts of MP-exposure on immunity vulnerability to HABs were investigated in the thick-shell mussel, Mytilus coruscus. Our results revealed evident immunotoxicity of MPs and P. lima to the mussel, as evidenced by significantly impaired total count, phagocytic activity, and cell viability of haemocytes, which may result from the induction of oxidative stress, aggravation of haemocyte apoptosis, and shortage in cellular energy supply. Moreover, marked disruptions of immunity, antioxidant system, apoptosis regulation, and metabolism upon MPs and P. lima exposure were illustrated by gene expression and comparative metabolomic analyses. Furthermore, the mussels that experienced MP-exposure were shown to be more vulnerable to P. lima, indicated by greater degree of deleterious effects on abovementioned parameters detected. In general, our findings emphasize the threat of MPs and HABs to bivalve species, which deserves close attention and more investigation.

Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury.

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. RESULTS: AAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). CONCLUSION: In the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.

In vivo absorption, in vitro simulated digestion and fecal fermentation properties of polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine and their effects on human gut microbiota.

Polysaccharides from Pinelliae Rhizoma Praeparatum Cum Alumine (PPA) have various biological activities, but their properties after oral administration are not clear. In this study, the absorption, digestion and fermentation properties of PPA were studied using in vivo fluorescence tracking, in vitro simulated digestion and fecal fermentation experiments. The absorption experiment showed that fluorescence was only observed in the gastrointestinal system, indicating that PPA could not be absorbed. Simulated digestion results showed that there were no significant changes in the molecular weight, Fourier transform infrared spectroscopy (FT-IR) spectrum, monosaccharides and reducing sugar of PPA during the digestion process, showing that the overall structure of PPA was not damaged. However, the carbohydrate gel electrophoresis bands of PPA enzymatic hydrolysates after simulated digestion were significantly changed, indicating that simulated digestion might impact the configuration of PPA. In vitro fermentation showed that PPA could be degraded by microorganisms to produce short chain fatty acids, leading to a decrease in pH value. PPA can promote the proliferation of Bacteroideaceae, Megasphaera, Bacteroideaceae, and Bifidobacteriaceae, and inhibit the growth of Desulfobacteriota and Enterobacteriaceae. The results indicated that PPA could treat diseases by regulating gut microbiota, providing a scientific basis for the application and development of PPA.

Correction: Chen et al. Multifunctional Injectable Hydrogel Loaded with Cerium-Containing Bioactive Glass Nanoparticles for Diabetic Wound Healing. Biomolecules 2021, 11, 702.

The authors would like to replace Figure 4A of the following published paper [...].

Relationship of microvascular complications and healthy lifestyle with all-cause and cardiovascular mortality in women compared with men with type 2 diabetes.

BACKGROUND: Sex differences exist in the prevalence of microvascular disease (MVD) and healthy-lifestyle adherence. Whether MVD and healthy lifestyles are associated with mortality risk similarly for women and men who have type 2 diabetes mellitus (T2DM) remains unknown. METHODS: The present study included 9992 women and 15,860 men with T2DM from the UK Biobank. MVDs included retinopathy, peripheral neuropathy, and chronic kidney disease. Healthy lifestyle factors consisted of ideal BMI, nonsmoking, healthy diet, regular exercise, and appropriate sleep duration. Sex-specific hazard ratios (HRs) of mortality associated with the MVDs or healthy lifestyles were calculated and women-to-men ratio of HRs (RHR) were further estimated, after multivariable adjustment for potential confounders. RESULTS: During a median of 12.7 years of follow-up, 4346 (1202 in women) all-cause and 1207 (254 in women) CVD deaths were recorded. The adjusted HRs (95% CI) of all-cause mortality for 1 additional increment of the MVDs were 1.71 (1.55, 1.88) for women and 1.48 (1.39, 1.57) for men, with an RHR of 1.16 (1.03, 1.30). The corresponding RHR was 1.36 (1.09, 1.69) for cardiovascular mortality. Adhering to a healthy lifestyle (≥4 vs. ≤1 lifestyle factor) was associated with an approximately 60%-70% lower risk of all-cause and cardiovascular mortality without sex differences (P-interaction >0.70). Furthermore, as compared with having no MVD and an unfavorable lifestyle, having ≥2 MVDs but a favorable lifestyle was not associated with a higher risk of all-cause mortality either in women (HR = 0.88; 95% CI: 0.49, 1.60) or in men (HR = 0.95; 95% CI: 0.64, 1.40), similarly when considering cardiovascular mortality. CONCLUSIONS: In T2DM, while MVDs are more strongly associated with mortality risk in women than in men, adhering to a favorable lifestyle is associated with a substantially lower risk of mortality and may eliminate the detrimental impact of MVDs in both sexes.

Microvascular burden and long-term risk of stroke and dementia in type 2 diabetes mellitus.

OBJECTIVE: To examine the associations between microvascular disease (MVD) and risk of stroke, dementia, and their major subtypes among individuals with type 2 diabetes mellitus (T2DM). METHODS: We included 26,173 participants with T2DM from the UK Biobank who had no known stroke or dementia at baseline. MVD burden was reflected by the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. Cox regression models were used to estimate hazard ratios (HRs) and 95 % confidential intervals (CIs) of stroke and dementia associated with overall MVD burden and individual MVD. RESULTS: During a median follow-up of 11.5 years, 1103 incident stroke (964 ischemic and 269 hemorrhagic stroke) and 813 incident dementia (312 Alzheimer's disease and 304 vascular dementia) cases were identified. The risk of stroke, dementia, and their major subtypes all increased with an increasing number of MVD (all P-trend <0.001). The adjusted HRs (95 % CIs) comparing three with no MVD were 5.03 (3.16, 8.02) for all stroke, 4.57 (2.75, 7.59) for ischemic stroke, and 6.60 (2.65, 16.43) for hemorrhagic stroke. The corresponding estimates were 4.28 (2.33, 7.86) for all-cause dementia, 6.96 (3.02, 16.01) for Alzheimer's disease, and 3.81 (1.40, 10.42) for vascular dementia. Among the three MVD, chronic kidney disease showed the strongest associations with both stroke subtypes, while peripheral neuropathy was most strongly associated with both dementia subtypes. CONCLUSIONS: Risk of stroke, dementia, and their major subtypes increased with an increasing number of MVD. The associations of individual MVD with stroke and dementia varied substantially by types of MVD.

A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Microvascular Disease, Cardiovascular Health, and Risk of Coronary Heart Disease in Type 2 Diabetes: A UK Biobank Study.

CONTEXT: The interplay between cardiovascular health metrics (CVHMs) and microvascular disease (MVD) in relation to the risk of incident coronary heart disease (CHD) among individuals with type 2 diabetes mellitus (T2DM) remains to be evaluated. OBJECTIVE: To investigate the role of MVD and CVHMs in the development of CHD among T2DM. DESIGN: We included 19,664 participants with T2DM from the UK Biobank who had data on CVH metrics (CVHMs) and were free of CHD during recruitment. CVHMs were defined based on five behavioral (body mass index, diet, sleep duration, smoking, and regular exercise) and three biological factors (glycemic control, hyperlipidemia, and hypertension). MVD was defined as the presence of retinopathy, peripheral neuropathy, and chronic kidney disease. HR and 95% CI of CHD were estimated by multivariable Cox regression models. RESULTS: There were 3,252 incident cases of CHD recorded after a median follow-up of 12.3 years. After multivariable adjustment, each MVD was separately associated with risk of CHD, and those who had 1 or ≥2 MVD had a 27% and an 87% increased risk of developing CHD, respectively. Each of the unfavorable CVHMs was associated with a higher risk of CHD. As compared with MVD-free participants who had ideal CVHMs, those who had ≥2 MVD and had poor CVHMs were at particularly high risk of incident CHD (HR=4.58; 95% CI: 3.58, 5.86), similarly when considering behavioral CVH or biological CVH separately. On an additive scale, there was a positive statistically significant interaction between number of MVD and CVHMs. CONCLUSIONS: Coexistence of multiple MVDs was associated with a substantially higher risk of CHD among individuals with T2DM. Such an association may be amplified by unfavorable CVHMs.

The great potential of polysaccharides from natural resources in the treatment of asthma: A review.

Despite significant progress in diagnosis and treatment, asthma remains a serious public health challenge. The conventional therapeutic drugs for asthma often have side effects and unsatisfactory clinical efficacy. Therefore, it is very urgent to develop new drugs to overcome the shortcomings of conventional drugs. Natural polysaccharides provide enormous resources for the development of drugs or health products, and they are receiving a lot of attention from scientists around the world due to their safety, effective anti-inflammatory and immune regulatory properties. Increasing evidence shows that polysaccharides have favorable biological activities in the respiratory disease, including asthma. This review provides an overview of primary literature on the recent advances of polysaccharides from natural resources in the treatment of asthma. The mechanisms and practicability of polysaccharides, including polysaccharides from plants, fungus, bacteria, alga, animals and others are reviewed. Finally, the further research of polysaccharides in the treatment of asthma are discussed. This review can provide a basis for further study of polysaccharides in the treatment of asthma and provides guidance for the development and clinical application of novel asthma treatment drugs.

Corrigendum to "Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors" [Genes Dis 10 (2023) 389-392].

[This corrects the article DOI: 10.1016/j.gendis.2022.07.001.].

Association of phthalate exposure with all-cause mortality across renal function status: The U.S. National Health and Nutrition Examination Survey, 2005-2018.

BACKGROUND: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear. METHODS: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status. RESULTS: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44). CONCLUSIONS: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

[COL4A5 genotypes and clinical characteristics of children with Alport syndrome]. / 儿童Alport综合征COL4A5åŸºå› åž‹åŠä¸´åºŠç‰¹ç‚¹åˆ†æž.

OBJECTIVES: To investigate the genotypes of the pathogenic gene COL4A5 and the characteristics of clinical phenotypes in children with Alport syndrome (AS). METHODS: A retrospective analysis was performed for the genetic testing results and clinical data of 19 AS children with COL4A5 gene mutations. RESULTS: Among the 19 children with AS caused by COL4A5 gene mutations, 1 (5%) carried a new mutation of the COL4A5 gene, i.e., c.3372A>G(p.P1124=) and presented with AS coexisting with IgA vasculitis nephritis; 3 children (16%) had large fragment deletion of the COL4A5 gene, among whom 2 children (case 7 had a new mutation site of loss51-53) had gross hematuria and albuminuria at the onset, and 1 child (case 13 had a new mutation site of loss3-53) only had microscopic hematuria, while the other 15 children (79%) had common clinical phenotypes of AS, among whom 7 carried new mutations of the COL4A5 gene. Among all 19 children, 3 children (16%) who carried COL4A5 gene mutations also had COL4A4 gene mutations, and 1 child (5%) had COL4A3 gene mutations. Among these children with double gene mutations, 2 had gross hematuria and proteinuria at the onset. CONCLUSIONS: This study expands the genotype and phenotype spectrums of the pathogenic gene COL4A5 for AS. Children with large fragment deletion of the COL4A5 gene or double gene mutations of COL4A5 with COL4A3 or COL4A4 tend to have more serious clinical manifestations.

Lipoprotein(a), family history of cardiovascular disease, and incidence of heart failure.

Lipoprotein(a) (Lp(a)) is a largely genetically determined biomarker for cardiovascular disease (CVD), while its potential interplay with family history (FHx) of CVD, a measure of both genetic and environmental exposures, remains unclear. We examined the associations of Lp(a) in terms of circulating concentration or polygenetic risk score (PRS), and FHx of CVD with risk of incident heart failure (HF). Included were 299,158 adults from the UK Biobank without known HF and CVD at baseline. Hazards ratios (HRs) and 95% Cls were estimated by Cox regression models adjusted for traditional risk factors defined by the Atherosclerosis Risk in Communities study HF risk score. During the 11.8-year follow-up, 5,502 incidents of HF occurred. Higher levels of circulating Lp(a), Lp(a) PRS, and positive FHx of CVD were associated with higher risks of HF. Compared with individuals who had lower circulating Lp(a) and no FHx, HRs (95% CIs) of HF were 1.36 (1.25, 1.49), 1.31 (1.19, 1.43), and 1.42 (1.22, 1.67) for those with higher Lp(a) and a positive history of CVD for all family members, parents, and siblings, respectively; similar results were observed by using Lp(a) PRS. The risk estimates for HF associated with elevated Lp(a) and positive FHx were attenuated after excluding those with incident myocardial infarction (MI) during follow-up. Lp(a) and FHx of CVD were independent risk factors for incident HF, and the highest risk of HF was observed among individuals with both risk factors. The association may be partly mediated by myocardial infarction.

Model-Independent Learning of Quantum Phases of Matter with Quantum Convolutional Neural Networks.

Quantum convolutional neural networks (QCNNs) have been introduced as classifiers for gapped quantum phases of matter. Here, we propose a model-independent protocol for training QCNNs to discover order parameters that are unchanged under phase-preserving perturbations. We initiate the training sequence with the fixed-point wave functions of the quantum phase and add translation-invariant noise that respects the symmetries of the system to mask the fixed-point structure on short length scales. We illustrate this approach by training the QCNN on phases protected by time-reversal symmetry in one dimension, and test it on several time-reversal symmetric models exhibiting trivial, symmetry-breaking, and symmetry-protected topological order. The QCNN discovers a set of order parameters that identifies all three phases and accurately predicts the location of the phase boundary. The proposed protocol paves the way toward hardware-efficient training of quantum phase classifiers on a programmable quantum processor.

Glomerular filtration rate estimated by differing measures and risk of all-cause mortality among Chinese individuals without or with diabetes: A nationwide prospective study.

BACKGROUND: Whether estimated glomerular filtration rates (eGFRs) by differing biomarkers are differentially associated with mortality or whether the associations differ by diabetes status remains unclear, especially in Chinese population. METHODS: We included 6995 participants without diabetes (mean age: 60.4 years) and 1543 with diabetes (mean age: 61.8 years). Each eGFR measure was divided into normal (≥90 mL/min/1.73 m2 ), modestly declined (60 to <90 mL/min/1.73 m2 ), and chronic kidney disease (CKD) (<60 mL/min/1.73 m2 ) groups. Cox proportional hazards models were used to estimate hazard ratio (HR) of all-cause mortality associated with each eGFR. RESULTS: Over a follow-up of 7 years, 677 and 215 deaths occurred among individuals without or with diabetes, respectively. Among those without diabetes, all measures of modestly declined eGFR were not associated with mortality, whereas CKD defined by eGFR cystatin C (eGFRcys) and eGFR creatinine (eGFRcr)-cys (HRs were 1.71 and 1.55, respectively) but not by eGFRcr were associated with higher risk of mortality. Among diabetes, all measures of modestly declined eGFR (HRs: 1.53, 1.56, and 2.09 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) and CKD (HRs: 2.57, 2.99, and 3.92 for eGFRcr, eGFRcys, and eGFRcr-cys, respectively) were associated with higher risk of mortality. Regardless of diabetes status, an addition of eGFRcys or eGFRcr-cys to traditional risk factors lead to a larger improvement in the prediction of all-cause mortality risk than adding eGFRcr. CONCLUSIONS: The association of eGFR with mortality risk appeared to be varied by its measures and by diabetes status among middle-aged and older Chinese, which needs to be considered in clinical practice.

Characterization of Polysaccharides from the Pericarp of Zanthoxylum bungeanum Maxim by Saccharide Mapping and Their Neuroprotective Effects.

The pericarp of Zanthoxylum bungeanum maxim (PZM) is a commonly used spice and herbal medicine in China. In the present study, the structural characteristics of PPZM were investigated by saccharide mapping after enzymatic digestion by using high-performance thin layer chromatography (HPTLC) and polysaccharide analysis by using carbohydrate gel electrophoresis (PACE). The mechanisms of protective effects of PPZM on Aß25-35-induced oxidative damage were explored in PC12 cells. The results showed that PPZM contained 1,4-α-D-galactosidic, 1,4-α-D-galactosiduronic, and (1→4)-ß-D-glucosidic linkages. Pretreatment with PPZM significantly increased the cell viability of Aß25-35-injured PC12 cells. Flow cytometry and Hoechst/PI staining indicated that PPZM gradually relieved the apoptosis of the Aß25-25-treated cells. PPZM markedly decreased the ROS level of PC12 cells and suppressed Aß25-35-induced oxidative stress by increasing the SOD level, and decreasing the level of MDA and LDH. The mRNA expressions of caspase-3 and Bax were significantly downregulated, and Bcl-2 expression was upregulated by treatment with PPZM. PPZM significantly increased the mRNA expression of Nrf2 and HO-1 in Aß25-35 treated cells. The results indicated that PPZM alleviated apoptosis and oxidative stress induced by Aß25-25 through the inhibition of mitochondrial dependent apoptosis and activation of Nrf2/HO-1 pathway. PPZM can be used as a potential protective agent against Aß25-25-induced neurotoxicity.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

A highly accumulated secretory protein from cotton bollworm interacts with basic helix-loop-helix transcription factors to dampen plant defense.

Caterpillar oral secretion (OS) contains active molecules that modulate plant defense signaling. We isolated an effector-like protein (Highly Accumulated Secretory Protein 1, HAS1) from cotton bollworm (Helicoverpa armigera) that is the most highly accumulated secretory protein of the nondigestive components in OS and belongs to venom R-like protein. Elimination of HAS1 by plant-mediated RNA interference reduced the suppression of OS on the defense response in plants. Plants expressing HAS1 are more susceptible to insect herbivory accompanied by the reduced expressions of multiple defense genes. HAS1 binds to the basic helix-loop-helix (bHLH) transcription factors, including GoPGF involved in pigmented gland formation and defense compounds biosynthesis in cotton and MYC3/MYC4 the main regulators in jasmonate (JA) signaling in Arabidopsis. The binding activity is required for HAS1 to inhibit the activation of bHLHs on plant defense gene expressions. Together with our previous study that another venom R-like protein HARP1 in cotton bollworm OS blocks JA signaling by interacting with JASMONATE-ZIM-domain repressors, we conclude that the venom R-like proteins in OS interfere with plant defense in a dual suppression manner. Considering the venom proteins in parasitic wasp assault the immune system of its host animal, our investigation reveals their conserved function in carnivorous and herbivorous insects.