Natural variation in WHITE-CORE RATE 1 regulates redox homeostasis in rice endosperm to affect grain quality.

Grain chalkiness reduces the quality of rice (Oryza sativa) and is a highly undesirable trait for breeding and marketing. However, the underlying molecular cause of chalkiness remains largely unknown. Here, we cloned the F-box gene WHITE-CORE RATE 1 (WCR1), which negatively regulates grain chalkiness and improves grain quality in rice. A functional A/G variation in the promoter region of WCR1 generates the alleles WCR1A and WCR1G, which originated from tropical japonica and wild rice Oryza rufipogon, respectively. OsDOF17 is a transcriptional activator that binds to the AAAAG cis-element in the WCR1A promoter. WCR1 positively affects the transcription of the metallothionein gene MT2b and interacts with MT2b to inhibit its 26S proteasome-mediated degradation, leading to decreased reactive oxygen species production and delayed programmed cell death in rice endosperm. This, in turn, leads to reduced chalkiness. Our findings uncover a molecular mechanism underlying rice chalkiness and identify the promising natural variant WCR1A, with application potential for rice breeding.

Reprogramming Tumor-Associated Macrophages with a Se-Based Core-Satellite Nanoassembly to Enhance Cancer Immunotherapy.

Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.

Bat-Origin Swine Acute Diarrhea Syndrome Coronavirus Is Lethal to Neonatal Mice.

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. We rescued synthetic wild-type SADS-CoV using one-step assembly of a viral cDNA clone by homologous recombination in yeast. Furthermore, we characterized SADS-CoV replication in vitro and in neonatal mice. We found that SADS-CoV caused severe watery diarrhea, weight loss, and a 100% fatality rate in 7- and 14-day-old mice after intracerebral infection. We also detected SADS-CoV-specific N protein in the brain, lungs, spleen, and intestines of infected mice. Furthermore, SADS-CoV infection triggers excessive cytokine expression that encompasses a broad array of proinflammatory mediators, including interleukin 1ß (IL-1ß), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), C-X-C motif chemokine ligand 10 (CXCL10), interferon beta (IFN-ß), IFN-γ, and IFN-λ3. This study highlights the importance of identifying neonatal mice as a model for developing vaccines or antiviral drugs against SADS-CoV infection. IMPORTANCE SADS-CoV is the documented spillover of a bat coronavirus that causes severe disease in pigs. Pigs are in frequent contact with both humans and other animals and theoretically possess a greater chance, compared to many other species, of promoting cross-species viral transmission. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Animal models are an essential feature of the vaccine design toolkit. Compared with neonatal piglets, the mouse is small, making it an economical choice for animal models for SADS-CoV vaccine design. This study showed the pathology of neonatal mice infected with SADS-CoV, which should be very useful for vaccine and antiviral studies.

Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives.

Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/ß-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

In Situ Polymerization for Manufacture of Multifunctional Delivery Systems for Transcellular Delivery of Nucleic Acids.

Electrostatic self-assembly between negatively charged nucleic acids and cationic materials is the basis for the formulation of the delivery systems. Nevertheless, structural disintegration occurs because their colloidal stabilities are frequently insufficient in a hostile biological environment. To overcome the sequential biological barriers encountered during transcellular gene delivery, we attempted to use in situ polymerization onto plasmid DNA (pDNA) with a variety of functional monomers, including N-(3-aminopropyl)methacrylate, (aminopropyl)methacrylamide hydrochloride, 1-vinylimidazole, and 2-methacryloyloxyethylphosphorylcholine and N,N'-bis(acryloyl) cystamine. The covalently linked monomers could polymerize into a network structure on top of pDNA, providing excellent structural stability. Additionally, the significant proton buffering capacity of 1-vinylimidazole is expected to aid in the release of pDNA payloads from acidic and digestive endolysosomes. In addition, the redox-mediated cleavage of the disulfide bond in N,N'-bis(acryloyl)cystamine allows for the selective cleavage of the covalently linked network in the cytosolic microenvironment. This is due to the high intracellular level of glutathione, which promotes the liberation of pDNA payloads in the cell interiors. The proposed polymerization strategies resulted in well-defined nanoscale pDNA delivery systems. Excellent colloidal stabilities were observed, even when incubated in the presence of high concentrations of heparin (10 mg/mL). In contrast, the release of pDNA was confirmed upon incubation in the presence of glutathione, mimicking the intracellular microenvironment. Cell transfection experiments verified their efficient cellular uptake and gene expression activities in the hard-transfected MCF-7 cells. Hence, the polymerization strategy used in the fabrication of covalently linked nonviral gene delivery systems shows promise in creating high-performance gene delivery systems with diverse functions. This could open new avenues in cellular microenvironment engineering.

Microalgal glycerol-3-phosphate acyltransferase role in galactolipids and high-value storage lipid biosynthesis.

Glycerolipids are the most abundant lipids in microalgae, and glycerol-3-phosphate:acyl-CoA acyltransferase (GPAT) plays an important role in their biosynthesis. However, the biochemical and biological functions of algal GPAT remain poorly characterized. Here, we characterized the endoplasmic reticulum (ER)-associated GPAT of the model unicellular green alga Chlamydomonas reinhardtii (CrGPATer). Enzymatic assays indicated that CrGPATer is an sn-1 acyltransferase using a variety of acyl-CoAs as the acyl donor. Subcellular localization revealed that CrGPATer was associated with ER membranes and lipid droplets. We constructed overexpression (OE) and knockdown (KD) transgenic C. reinhardtii lines to investigate the in vivo function of CrGPATer. Lipidomic analysis indicated that CrGPATer OE enhanced the cellular content of galactolipids, especially monogalactosyldiacylglycerol, under nitrogen deficiency stress. Correspondingly, CrGPATer KD lines contained lower contents of galactolipids than the control. Feeding experiments with labeled phosphatidic acid revealed that the intermediate of the eukaryotic Kennedy pathway could be used for galactolipid biosynthesis in the chloroplasts. These results provided multiple lines of evidence that the eukaryotic Kennedy pathway mediated by CrGPATer may be involved in galactolipid biosynthesis in C. reinhardtii. OE of CrGPATer significantly increased the content of triacylglycerol and the yield of biomass. Moreover, the content and yield of 1, 3-olein-2-palmitin, a high-value lipid that can be used as an alternative for human milk fat in infant formula, were significantly enhanced in the OE transgenic lines. Taken together, this study provided insights into the biochemical and biological functions of CrGPATer and its potential as a genetic engineering target in functional lipid manufacturing.

The relationship between resistance evolution and carbon metabolism in Staphylococcus xylosus under ceftiofur sodium stress.

Staphylococcus xylosus has emerged as a bovine mastitis pathogen with increasing drug resistance, resulting in substantial economic impacts. This study utilized iTRAQ analysis to investigate the mechanisms driving resistance evolution in S. xylosus under ceftiofur sodium stress. Findings revealed notable variations in the expression of 143 proteins, particularly glycolysis-related proteins (TpiA, Eno, GlpD, Ldh) and peptidoglycan (PG) hydrolase Atl. Following the induction of ceftiofur sodium resistance in S. xylosus, the emergence of resistant strains displaying characteristics of small colony variants (SCVs) was observed. The transcript levels of TpiA, Eno, GlpD and Ldh were up-regulated, TCA cycle proteins (ICDH, MDH) and Atl were down-regulated, lactate content was increased, and NADH concentration was decreased in SCV compared to the wild strain. That indicates a potential role of carbon metabolism, specifically PG hydrolysis, glycolysis, and the TCA cycle, in the development of resistance to ceftiofur sodium in S. xylosus.

QTL detection for grain shape and fine mapping of two novel locus qGL4 and qGL6 in rice.

Rice grain size and grain weight, which have a great influence on rice quality and yield, are complex quantitative traits that are mediated by grain length (GL), grain width (GW), length-to-width ratio (LWR), and grain thickness (GT). In this study, the BC1F2 and BC1F2:3 populations derived from a cross between two indica rice varieties, Guangzhan 63-4S (GZ63-4S) and Dodda, were used to locate quantitative trait loci (QTL) related to grain size. A total of 30 QTL associated with GL, GW and LWR were detected, of which six QTL were scanned repeatedly in both populations. Two QTL, qGL4 and qGL6, were selected for genetic effect validation and were subsequently fine mapped to 2.359 kb and 176 kb, respectively. LOC_Os04g52240 (known as OsKS2/OsKSL2), which encoding an ent-beyerene synthase and as the only gene found in 2.359 kb interval, was proposed to be the candidate for qGL4. Moreover, the grains of qGL4 homozygous mutant plants generated by the CRISPR-Cas9 system became shorter and wider. In addition, the qGL4 allele from GZ63-4S contributes to the increase of yield per plant. Our study not only laid the foundation for further functional study of qGL4 and map-based cloning of qGL6, but also provided genetic resources for the development of high yield and good quality rice varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01502-8.

Apheresis practice variation during the COVID-19 pandemic: Results of a survey.

BACKGROUND: The COVID-19 pandemic affected healthcare delivery across all specialties including apheresis. To describe the changes in apheresis service practices that occurred during the pandemic, the American Society for Apheresis (ASFA) Apheresis Medicine Attending Physician Subcommittee conducted a survey study. STUDY DESIGN AND METHODS: A 32-question survey was designed and distributed to 400 ASFA physician members on September 7, 2022. Attending physicians responded to questions about whether and how apheresis service practices changed during the COVID-19 pandemic compared with the time period prior to the pandemic in terms of: (1) procedure types and volumes, (2) patient consultation workflow, and (3) the use of telemedicine. Descriptive analyses were reported as number and frequency of responses. RESULTS: The survey response rate was 13.8% (55/400). Of these respondents, 96.4% (53/55) were attending physicians. The majority of respondents (42/53, 79.2%) indicated that the types of procedures performed during COVID-19 compared to pre-pandemic did not change. Most frequently for apheresis procedure volume, respondents reported: no change in their monthly inpatient volume (21/47, 44.7%) and a decrease in their monthly outpatient volume (28/46, 60.9%). Prior to COVID-19, 75.0% (30/40) of respondents performed consultations at bedside for inpatients and 67.4% (29/43) performed consultations at bedside for outpatients. Bedside consultations decreased in both settings during the pandemic but were still most frequently performed by attending physicians. At the same time, the use of telemedicine increased for 15.4% of survey respondents during COVID-19. CONCLUSION: Some, but not all, respondents observed or made changes to their apheresis service during the COVID-19 pandemic. A subset of changes, such as increased utilization of telemedicine, may persist.

Fine Mapping of Five Grain Size QTLs Which Affect Grain Yield and Quality in Rice.

Grain size is a quantitative trait with a complex genetic mechanism, characterized by the combination of grain length (GL), grain width (GW), length to width ration (LWR), and grain thickness (GT). In this study, we conducted quantitative trait loci (QTL) analysis to investigate the genetic basis of grain size using BC1F2 and BC1F2:3 populations derived from two indica lines, Guangzhan 63-4S (GZ63-4S) and TGMS29 (core germplasm number W240). A total of twenty-four QTLs for grain size were identified, among which, three QTLs (qGW1, qGW7, and qGW12) controlling GL and two QTLs (qGW5 and qGL9) controlling GW were validated and subsequently fine mapped to regions ranging from 128 kb to 624 kb. Scanning electron microscopic (SEM) analysis and expression analysis revealed that qGW7 influences cell expansion, while qGL9 affects cell division. Conversely, qGW1, qGW5, and qGW12 promoted both cell division and expansion. Furthermore, negative correlations were observed between grain yield and quality for both qGW7 and qGW12. Nevertheless, qGW5 exhibited the potential to enhance quality without compromising yield. Importantly, we identified two promising QTLs, qGW1 and qGL9, which simultaneously improved both grain yield and quality. In summary, our results laid the foundation for cloning these five QTLs and provided valuable resources for breeding rice varieties with high yield and superior quality.

[Clinical and genetic analysis of a Chinese patient with Alström syndrome].

OBJECTIVE: To explore the genetic etiology for a patient with Alström syndrome (ALMS) presenting as dilated cardiomyopathy. METHODS: A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis. RESULTS: The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+PM2_Supporting+PM3+PP3, PVS1_VeryStrong+PM2_Supporting+PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. CONCLUSION: The c.6823C>T (p.Arg2275Ter) and c.9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

[Clinical Efficacy of Anchor Suture Bridge Technique for Avulsion Fractures of the Posterior Cruciate Ligament Tibial Insertion Point in the Knee Joint]. / é”šé’‰ç¼çº¿æ¡¥æŠ€æœ¯å¯¹è†å ³èŠ‚åŽäº¤å‰éŸ§å¸¦èƒ«éª¨æ­¢ç‚¹æ’•è„±éª¨æŠ˜çš„ä¸´åºŠç–—æ•ˆ.

Objective: To investigate the clinical efficacy of the anchor suture bridge technique in treating avulsion fractures at the tibial insertion point of the posterior cruciate ligament (PCL) in the knee joint. Methods: In this study, we reviewed 80 patients with PCL tibial avulsion fractures treated using the anchor suture bridge technique in our department from February 2010 to December 2023. Follow-ups were conducted starting at 3 months post-surgery, then every 3 months until 12 months post-surgery. Clinical and follow-up data of each patient were analyzed. The Lysholm and Hospital for Special Surgery Knee-Rating Scale (HSS) scores of knee function before surgery and at the last follow-up were compared to assess the surgical treatment outcome. Results: The 80 patients were followed up for an average of (12.16±1.08) months post-surgery. Re-examination X-rays showed that all fractures had healed, with an average healing time of (3.66±0.51) months. All patients recovered well, with primary healing of surgical incisions and no complications such as neurovascular injury, skin necrosis, incision infection, fracture displacement, or ligament laxity. Postoperative knee Lysholm and HSS scores were significantly higher than preoperative scores. At the last follow-up, the Lysholm score increased from (46.30±6.10) preoperatively to (90.85±3.27), and the HSS score increased from (45.30±5.80) to (91.15±2.66), with statistically significant differences (P<0.025). Conclusion: The anchor suture bridge technique is effective in treating avulsion fractures of the PCL tibial insertion point in the knee joint. It has a high safety profile and leads to good postoperative knee function recovery, with no serious postoperative complications, demonstrating excellent clinical efficacy.

MiR-652-3p promotes malignancy and metastasis of cancer cells via inhibiting TNRC6A in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was one of the most prevalent life-threatening cancers. Metastasis is the leading cause of cancer-related death in HCC. MiRNAs play essential roles in cancer metastasis. METHODS: Expression of miR-652-3p in HCC was assessed. Function experiments of miR-652-3p and trinucleotide repeat-containing gene 6A protein (TNRC6A) were performed both in vitro and in vivo. mRNA sequencing, PCR, and western blot were performed to verify the target genes and pathway of miR-652-3p. The lung metastasis and xenograft cancer model in nude mice was established to investigate the effects of the miR-652-3p and TRNC6A on tumor metastasis in vivo. The relationship between the expression of the miR-652-3p, TNRC6A and the prognosis of HCC patients was analyzed. RESULTS: Upregulated miR-652-3p was found in the tumor tissues of HCC, especially in metastatic HCC patients. Overexpression of miR-652-3p promoted and knockdown of miR-652-3p suppressed HCC metastasis both in vitro and in vivo. MiR-652-3p promoted HCC metastasis via regulating the EMT pathway. TNRC6A was identified as a direct target of miR-652-3p, and the knockdown of TNRC6A restored repressed EMT and HCC metastasis caused by the inhibition of miR-652-3p. Clinical results revealed that high expression of miR-652-3p and low expression of TNRC6A were positively correlated to shortened overall survival and disease-free survival in HCC patients. CONCLUSIONS: MiR-652-3p promotes EMT and HCC metastasis by inhibiting TNRC6A expression in HCC. MiR-652-3p and TNRC6A may serve as potential biomarkers to predict prognosis in HCC patients with metastasis.

A swine arterivirus deubiquitinase stabilizes two major envelope proteins and promotes production of viral progeny.

Arteriviruses are enveloped positive-strand RNA viruses that assemble and egress using the host cell's exocytic pathway. In previous studies, we demonstrated that most arteriviruses use a unique -2 ribosomal frameshifting mechanism to produce a C-terminally modified variant of their nonstructural protein 2 (nsp2). Like full-length nsp2, the N-terminal domain of this frameshift product, nsp2TF, contains a papain-like protease (PLP2) that has deubiquitinating (DUB) activity, in addition to its role in proteolytic processing of replicase polyproteins. In cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), nsp2TF localizes to compartments of the exocytic pathway, specifically endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi complex. Here, we show that nsp2TF interacts with the two major viral envelope proteins, the GP5 glycoprotein and membrane (M) protein, which drive the key process of arterivirus assembly and budding. The PRRSV GP5 and M proteins were found to be poly-ubiquitinated, both in an expression system and in cells infected with an nsp2TF-deficient mutant virus. In contrast, ubiquitinated GP5 and M proteins did not accumulate in cells infected with the wild-type, nsp2TF-expressing virus. Further analysis implicated the DUB activity of the nsp2TF PLP2 domain in deconjugation of ubiquitin from GP5/M proteins, thus antagonizing proteasomal degradation of these key viral structural proteins. Our findings suggest that nsp2TF is targeted to the exocytic pathway to reduce proteasome-driven turnover of GP5/M proteins, thus promoting the formation of GP5-M dimers that are critical for arterivirus assembly.

Presurgical MRI-Based Radiomics Models for Predicting Cerebellar Mutism Syndrome in Children With Posterior Fossa Tumors.

BACKGROUND: Current studies have indicated that tumoral morphologic features are associated with cerebellar mutism syndrome (CMS), but the radiomics application in CMS is scarce. PURPOSE: To develop a model for CMS discrimination based on multiparametric MRI radiomics in patients with posterior fossa tumors. STUDY TYPE: Retrospective. POPULATION: A total of 218 patients (males 132, females 86) with posterior fossa tumors, 169 of which were included in the MRI radiomics analysis. The MRI radiomics study cohort (169) was split into training (119) and testing (50) sets with a ratio of 7:3. FIELD/SEQUENCE: All the MRI were acquired under 1.5/3.0 T scanners. T2-weighted image (T2W), T1-weighted (T1W), fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI). ASSESSMENT: Apparent diffusion coefficient (ADC) maps were generated from DWI. Each MRI dataset generated 1561 radiomics characteristics. Feature selection was performed with univariable logistic analysis, correlation analysis, and least absolute shrinkage and selection operator (LASSO) penalized logistic regression. Significant clinical features were selected with multivariable logistic analysis and used to constructed the clinical model. Radiomics models (based on T1W, T2W, FLAIR, DWI, ADC) were constructed with selected radiomics features. The mix model was based on the multiparametric MRI radiomics features. STATISTICAL TEST: Multivariable logistic analysis was utilized during clinical features selection. Models' performance was evaluated using the area under the receiver operating characteristic (AUC) curve. Interobserver variability was assessed using Cohen's kappa. Significant threshold was set as P < 0.05. RESULTS: Sex (aOR = 3.72), tumor location (aOR = 2.81), hydrocephalus (aOR = 2.14), and tumor texture (aOR = 5.08) were significant features in the multivariable analysis and were used to construct the clinical model (AUC = 0.79); totally, 33 radiomics features were selected to construct radiomics models (AUC = 0.63-0.93). Seven of the 33 radiomics features were selected for the mix model (AUC = 0.93). DATA CONCLUSION: Multiparametric MRI radiomics may be better at predicting CMS than single-parameter MRI models and clinical model. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: 2.

Apheresis medicine education during the early phase of the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic introduced challenges and disruption across healthcare, including apheresis medicine (AM). In this study, we report findings from a survey conducted among American Society for Apheresis Physician Committee (ASFA-PC) members to describe the impact of the COVID-19 pandemic on AM education practices. STUDY DESIGN AND METHODS: A voluntary, anonymous, 24-question, institutional review board-approved survey regarding AM teaching during the pandemic was distributed to ASFA-PC members in the United States between December 1, 2020, and December 15, 2020. Descriptive analyses were reported as number and frequency of respondents for each question. Free text responses were summarized. RESULTS: Responses were received from 14/31 (45%) of ASFA-PC members, of whom 12 practiced at academic institutions. Among these, 11/12 (92%) transitioned to virtual platform for AM trainee conferences during the pandemic. A variety of resources were employed to support independent AM learning. While 7/12 (58%) respondents did not change the informed consent process for AM procedures, others delegated this process or introduced remote alternatives. The most common method respondents used to conduct AM patient rounding was a hybrid in-person/virtual model. CONCLUSION: This survey describes the adaptations and changes AM practitioners made to trainee education in response to the early phase of the COVID-19 pandemic. The transition to virtual and/or hybrid trainee learning and AM rounds underscores the importance of digital AM resources. Further study of the effects of the pandemic and its impact on AM trainee education, as well as patient care is warranted.

GrpE and ComD contribute to the adherence, biofilm formation, and pathogenicity of Streptococcus suis.

Streptococcus suis is a major bacterial pathogen of swine and an emerging zoonotic agent that has to date resulted in substantial economic losses to the swine industry worldwide, and can cause persistent infection by forming biofilms. GrpE and histidine protein kinase ComD are important proteins implicated in the pathogenicity of S. suis, although whether they play roles in adhesion and biofilm formation has yet to be sufficiently clarified. In this study, we constructed grpE and comD deletion strains of S. suis by homologous recombination, and examined their cell adhesion and biofilm formation capacities compared with those of the wild-type strain. The pathogenicity of the grpE and comD deletion strains was evaluated using a mouse infection model, which revealed that compared with the wild-type, these deletion strains induced milder symptoms and lower bacteremia, as well as comparatively minor organ (brain, spleen, liver, and lung) lesions, in the infected mice. Moreover, the deletion of grpE and comD significantly reduced the pro-inflammatory cytokine (IL-6, IL-1ß, and TNF-α) induction capacity of S. suis. Collectively, the findings of this study indicate that the GrpE and ComD proteins of Streptococcus suis play key roles in the adherence to PK-15 cells and the formation of biofilms, thereby contributing to the virulence of this pathogen.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

Imaging strategies for receptor tyrosine kinase dimers in living cells.

Receptor tyrosine kinases (RTKs) are the essential regulators of cell signal transduction pathways and play important roles in biological processes. RTK dimerization is generally considered the first step in receptor activation and cell communication. And the abnormal expression of RTK dimers is closely related to the occurrence and development of many diseases. Therefore, the visualization of RTK dimerization is of great significance for monitoring physiological processes. The genetic and nongenetic imaging strategies have attracted widespread attention due to their high efficiency and high sensitivity. In this review, the RTKs and their dimers as well as the advances in strategies for imaging RTK dimers are introduced. Furthermore, we analyze the limitations of existing imaging strategies and put forward suggestions for the future development of imaging probes. We expect that this review will inspire more in-depth investigation of RTK dimers, which will also broaden the application of strategies of RTK dimers in biomedical areas.

The WUR0000125 PRRS resilience SNP had no apparent effect on pigs' infectivity and susceptibility in a novel transmission trial.

BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) remains one of the most important infectious diseases for the pig industry. A novel small-scale transmission experiment was designed to assess whether the WUR0000125 (WUR for Wageningen University and Research) PRRS resilience single nucleotide polymorphism (SNP) confers lower susceptibility and infectivity to pigs under natural porcine reproductive and respiratory syndrome virus (PRRSV-2) transmission. METHODS: Commercial full- and half-sib piglets (n = 164) were assigned as either Inoculation, Shedder, or Contact pigs. Pigs were grouped according to their relatedness structure and WUR genotype, with R- and R+ referring to pigs with zero and one copy of the dominant WUR resilience allele, respectively. Barcoding of the PRRSV-2 strain (SD09-200) was applied to track pig genotype-specific transmission. Blood and nasal swab samples were collected and concentrations of PRRSV-2 were determined by quantitative (q)-PCR and cell culture and expressed in units of median tissue culture infectious dose (TCID50). The Log10TCID50 at each sampling event, derived infection status, and area under the curve (AUC) were response variables in linear and generalized linear mixed models to infer WUR genotype differences in Contact pig susceptibility and Shedder pig infectivity. RESULTS: All Shedder and Contact pigs, except one, became infected through natural transmission. There was no significant (p > 0.05) effect of Contact pig genotype on any virus measures that would indicate WUR genotype differences in susceptibility. Contact pigs tended to have higher serum AUC (p = 0.017) and log10TCID50 (p = 0.034) when infected by an R+ shedder, potentially due to more infectious R+ shedders at the early stages of the transmission trial. However, no significant Shedder genotype effect was found in serum (p = 0.274) or nasal secretion (p = 0.951) that would indicate genotype differences in infectivity. CONCLUSIONS: The novel design demonstrated that it is possible to estimate genotype effects on Shedder pig infectivity and Contact pig susceptibility that are not confounded by family effects. The study, however, provided no supportive evidence that genetic selection on WUR genotype would affect PRRSV-2 transmission. The results of this study need to be independently validated in a larger trial using different PRRSV strains before dismissing the effects of the WUR marker or the previously detected GBP5 gene on PRRSV transmission.