First Detection of Atractylodes Mild Mottle Virus in Atractylodes lancea (Thunb.) DC. in Hubei Province of China.

The cultivated aromatic medicinal herb Atractylodes lancea (Thunb.) DC. is widely used in the pharmaceuticals, nutraceuticals, and cosmetics industries (Na-Bangchang et al. 2014; Zhan et al. 2023). Huanggang in Hubei Province is a major production area for A. lancea (Huang et al. 2022; Wang et al. 2023). In April 2023, more than two-thirds of the surveyed plant leaves in this region exhibited virus-like symptoms, such as curling and mosaic patterns. To identify the underlying cause, 80 symptomatic plant leaf samples were collected from four fields (20 leaves per field) in this region and pooled for virome analysis. Total RNA, including ribosomal RNA, was extracted from the pooled samples using the Plant RNA Extraction Mini Kit (Onrew Biotech, Guangdong, China), for sequencing library construction. The Illumina NovaSeq 6000 platform was used to sequence the library and generate 150 bp paired-end reads. After processing the raw data with Trimmomatic software, a total of 44,354,650 high-quality clean reads were obtained. The clean reads were aligned against ribosomal RNA using BWA software (v0.7.17) to avoid interference and eliminate corresponding sequences. After removing potential contamination, contig assembly of the clean reads was performed using Megahit software (v1.2.9). The resulting contigs were compared with the virus NT database using the BLASTn program. Sequence pairwise comparison revealed 8 contigs (574 nt to 2243 nt) with identities ranging from 81.88% to 90.77% with Atractylodes mild mottle virus (AMMV, NC_027924.1, Lim et al., 2015). Additionally, contigs mapped to Carlavirus, Pelarspovirus, and other plant viruses in our virome dataset had low coverage and pairwise identity (less than 70%), which need to be further investigated. The presence of AMMV was confirmed by aligning the clean reads to the reference sequence (NC_027924.1) using BWA and SAMtools software, resulting in a consensus sequence (8024 nt) with gaps. DNA extraction from the pooled samples was performed using the Rapid Universal Genomic DNA Extraction Kit (Simgen, Zhejiang, China). Two pairs of specific primers, 3399F (5'-AAAGAAGAACCTCCTGATACGG-3')/5924R (5'-TGAACCTGATTCTCTTGGC-3') and 1830F (5'- CTCAGGAAATCCCAATGC -3')/3640R(5'-TTTCCCAATGTTCTTCGGG-3'), were designed to amplify the complete gene sequences of polymerase and coat protein (CP), based on the consensus sequence. The PCR products with the lengths of 2521 bp and 1814 bp were cloned into the pMD18-T vector (Takara Biotech, Dalian, China) for sequencing. The BLASTn analysis showed that the polymerase and CP gene sequences shared an identity of 94.51% (1929/2041 nt) and 88.41% (1419/1605 nt) with the AMMV isolate (NC_027924.1), respectively. The sequences have been deposited in GenBank under the accession numbers OR544810 and OR544811. We collected leaves from 32 A. lancea plants (16 symptomatic and 16 asymptomatic) in the fields. RT-PCR was conducted using CPF (5'-CTGCGAATATGAAAGTGC-3') and CPR (5'-GGTGAGCTTGTCTGTTAGG-3') primers, which were designed targeting a 527bp fragment of the CP gene (OR544811). Amplicons of the expected size (527bp) were detected in 24 plants (11 symptomatic and 13 asymptomatic), three of which were sequenced by Sanger sequencing, showing a 100% match to OR544811. These findings indicate that AMMV is prevalent in the major production area of A. lancea. Further research is needed to better characterize the potential risks of AMMV to A. lancea cultivation in China as well as other countries.

Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study.

Background: Significant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients. Methods: In our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis. Results: A total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups. Conclusions: Hepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.

Effects of saponins Rb1 and Re in American ginseng combined intervention on immune system of aging model.

Aging is a major risk factor for the development of many pathological processes, such as reduced immunity, cancer, cardiovascular diseases or neurodegenerative diseases, while age-related chronic diseases are the most common causes of death. This paper studies the effects of American ginseng saponin Rb1 and Re alone and combined intervention on the immune system of aging mouse models, by using 30 mg/kg Rb1, 15 mg/kg Re, and Rb1 + Re (30 mg/kg Rb1 and 15 mg/kg Re (co-intervention) was used to intervene in the aging model, and immune indicators such as thymus index, spleen index, interleukin and interferon were detected to evaluate the impact of Rb1 and Re on immune function. The results show that Rb1 and Re intervention alone can increase the spleen index by 7%-12% and the thymus index by 12%-19% in the aging model. After Rb1 or Re alone intervened, the apoptotic cells in the thymus were slightly reduced, and the proportion of apoptotic cells was reduced. The combination of Rb1 + Re can promote the thymus index and spleen index to increase by 23.40% and 25.5% respectively, which is more advantageous than Rb1 or Re alone. In addition, Rb1 and Re intervention can reduce the level of interferon INF to a level comparable to that of young mice. Rb1 + Re can not only reduce the INF content, but also reduce the TNF content. The above results show that American ginseng saponin Rb1 and Re can delay the decline of the immune system in the aging model, and the combined intervention of the two is significantly better than individual intervention in the recovery of the immune system. This paper can provide theoretical basis and data support for the development of American ginseng nutritional supplements and its application in aging groups products to improve immunity.

Physicochemical and antioxidant properties of pectin from Actinidia arguta Sieb.et Zucc (A. arguta) extracted by ultrasonic.

Pectin was extracted from Actinidia arguta Sieb. et Zucc (A.arguta) using the ultrasound-assisted acid method and the single acid method. The physicochemical properties, structure, and antioxidant properties of two different pectins were investigated. The results showed that the extraction yield of the ultrasound-assisted acid method is higher than that of the single acid method. The molecular structure of A. arguta pectin extracted by the ultrasound-assisted acid method belongs to a mixed structure of RG-I and HG-type domains. Through structural feature analysis, the ultrasound-assisted extraction pectin (UAP) has a more branched structure than the single acid-extracted pectin (SAP). The SAP has a higher degree of esterification than the UAP. The physical property results show that the viscosity, solubility, and water-holding capacity of the UAP are better than those of the SAP. The antioxidant test results show that the hydroxyl radical scavenging and reducing powers of the UAP are superior to those of the SAP. This study shows the composition, physicochemical properties, and antioxidant activity of A. arguta pectin extracted by the ultrasonic-assisted extraction method to provide a theoretical basis for its application as an antioxidant and other food additives in the food industry.

Enantioselective Construction of Chiral THIQUINOL and Its Derivatives via Chiral Phosphoric Acid Catalysis.

The first catalytic enantioselective construction of chiral THIQUINOL and its derivatives has been accomplished through a chiral phosphoric-acid-catalyzed direct aza-Friedel-Crafts reaction of 3,4-dihydroisoquinolines with 2-naphthols/anthracen-2-ols/phenanthren-9-ol. This method offers a powerful and straightforward synthetic route toward chiral THIQUINOL derivatives with good to excellent yields and enantioselectivities. These structural motifs are crucial chiral components for further transformations into established or potential chiral ligands and catalysis.

Associative role of HLA-DRB1 as a protective factor for susceptibility and progression of Parkinson's disease: a Chinese cross-sectional and longitudinal study.

Background: Previous genome-wide association studies investigating the relationship between the HLA-DRB1 and the risk of Parkinson's disease (PD) have shown limited racial diversity and have not explored clinical heterogeneity extensively. Methods: The study consisted of three parts: a case-control study, a cross-sectional study, and a longitudinal cohort study. The case-control study included 477 PD patients and 477 healthy controls to explore the relationship between rs660895 and PD susceptibility. The cross-sectional study utilized baseline data from 429 PD patients to examine the correlation between rs660895 and PD features. The longitudinal study included 388 PD patients who completed a 3-year follow-up to investigate the effects of rs660895 on PD progression. Results: In the case-control study, HLA-DRB1 rs660895-G allele was associated with a decreased risk of PD in allele model (adjusted OR=0.72, p = 0.003) and dominant model (AG + GG vs. AA: adjusted OR = 0.67, p = 0.003). In the cross-sectional analysis, there was no association between rs660895 and the onset age, motor phenotype, or initial motor symptoms. In the longitudinal analysis, PD patients with the G allele exhibited a slower progression of motor symptoms (MDS-UPDRS-III total score: ß = -5.42, p < 0.001, interaction ptime × genotype < 0.001) and non-motor symptoms (NMSS score: ß = -4.78, p = 0.030, interaction ptime × genotype < 0.001). Conclusion: Our findings support HLA-DRB1 rs660895-G allele is a protective genetic factor for PD risk in Chinese population. Furthermore, we also provide new evidence for the protective effect of rs660895-G allele in PD progression.

Quantum interference enhances the performance of single-molecule transistors.

Quantum effects in nanoscale electronic devices promise to lead to new types of functionality not achievable using classical electronic components. However, quantum behaviour also presents an unresolved challenge facing electronics at the few-nanometre scale: resistive channels start leaking owing to quantum tunnelling. This affects the performance of nanoscale transistors, with direct source-drain tunnelling degrading switching ratios and subthreshold swings, and ultimately limiting operating frequency due to increased static power dissipation. The usual strategy to mitigate quantum effects has been to increase device complexity, but theory shows that if quantum effects can be exploited in molecular-scale electronics, this could provide a route to lower energy consumption and boost device performance. Here we demonstrate these effects experimentally, showing how the performance of molecular transistors is improved when the resistive channel contains two destructively interfering waves. We use a zinc-porphyrin coupled to graphene electrodes in a three-terminal transistor to demonstrate a >104 conductance-switching ratio, a subthreshold swing at the thermionic limit, a >7 kHz operating frequency and stability over >105 cycles. We fully map the anti-resonance interference features in conductance, reproduce the behaviour by density functional theory calculations and trace back the high performance to the coupling between molecular orbitals and graphene edge states. These results demonstrate how the quantum nature of electron transmission at the nanoscale can enhance, rather than degrade, device performance, and highlight directions for future development of miniaturized electronics.

Correlation of preoperative frailty with postoperative delirium and one-year mortality in Chinese geriatric patients undergoing noncardiac surgery: Study protocol for a prospective observational cohort study.

BACKGROUND: To Frailty is associated with postoperative delirium (POD) but is rarely assessed in patients undergoing noncardiac surgery. In this study, the correlation between preoperative frailty and POD, one-year mortality will be investigated in noncardiac Chinese geriatric surgery patients. METHODS: This study is a prospective, observational, cohort study conducted at a single center with Chinese geriatric patients. Patients who undergo noncardiac surgery and are older than 70 years will be included. A total of 536 noncardiac surgery patients will be recruited from the First Affiliated Hospital of Shandong First Medical University for this study. The Barthel Index (BI) rating will be used to assess the patient's ability to carry out everyday activities on the 1st preoperative day. The modified frailty index (mFI) will be used to assess frailty. Patients in the nonfrailty group will have an mFI < 0.21, and patients in the frailty group will have an mFI ≥ 0.21. The primary outcome is the incidence of POD. Three-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM) will be conducted twice daily during the 1st-7th postoperative days, or just before discharge. The secondary outcomes will include one-year mortality, in-hospital cardiopulmonary events, infections, acute renal injury, and cerebrovascular events. DISCUSSION: This study will clarify the correlation of preoperative frailty with POD and one-year all-cause mortality in Chinese geriatric patients undergoing noncardiac surgery. Can preoperative frailty predict POD or one-year mortality? In the face of China's serious aging social problems, this result may have important clinical value for the surgical treatment of geriatric patients. TRIAL REGISTRATION: This protocol has been registered with ClinicalTrials. Gov on 12 January 2022 (https://clinicaltrials.gov/ct2/show/NCT05189678).

Association between preoperative frailty and myocardial injury after noncardiac surgery in geriatric patients: study protocol for a prospective, multicentre, real-world observational, cohort trial.

INTRODUCTION: Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. METHODS AND ANALYSIS: This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. DISCUSSION: This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. CLINICAL TRIAL REGISTRATION: https://beta. CLINICALTRIALS: gov/study/NCT05635877 , NCT05635877.

Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease.

Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.

Iron overload increases the sensitivity of endometriosis stromal cells to ferroptosis via a PRC2-independent function of EZH2.

Given the high concentration of iron in the micro-environment of ovarian endometriosis, it is plausible to hypothesize that ectopic endometrial cells may be more susceptible to undergoing ferroptosis. Manipulation of ferroptosis has been explored as a potential therapeutic strategy to treat related diseases. In this study, we examined the impact on ectopic endometrial stromal cells (EESCs) of iron overload and an inducer of ferroptosis. We found that the iron concentration in the ovarian endometriosis was much higher than control samples. Treatment of cultured EESCs with ferric ammonium citrate (FAC) increase the sensitivity to undergo ferroptosis. By analyzing the RNA-seq results, it was discovered that zeste 2 polycomb repressive complex 2 subunit (EZH2) was significantly downregulated in ferroptosis induced EESCs. Moreover, overexpression of EZH2 effectively prevented the induction of ferroptosis. In addition, the activity or expression of EZH2 is directly and specifically inhibited by the methyltransferase inhibitor GSK343, which raises the sensitivity of stromal cells to ferroptosis. Taken together, our findings revealed that EZH2 act as a suppressor in the induced cell ferroptosis through a PRC2-independent methyltransferase mechanism. Therefore, blocking EZH2 expression and inducing ferroptosis may be effective treatment approaches for ovarian endometriosis.

Quantitating myocardial fibrosis using extracellular extravascular volume determined from computed tomography myocardial perfusion imaging.

PURPOSE: Both of extracellular extravascular volume (EEV) and extracellular volume fraction (ECV) were proposed to quantify enlargement of myocardial interstitial space due to myocardium loss or fibrosis. The study aimed to investigate the feasibility of using EEV derived from myocardial computed tomography (CT) perfusion imaging (VPCT) and extracellular volume quantification with single-energy subtraction CT (ECV- SECT) for quantifying myocardial fibrosis. METHODS: In this study, 17 patients with suspected and known coronary artery disease underwent examination using a dual-source CT scanner. The EEV- VPCT was derived from dynamic whole-heart myocardial perfusion imaging, and the ECV_SECT was calculated from late-enhanced images 5 min after bolus contrast injection by subtracting the noncontrast baseline. The late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging was used as a reference. RESULTS: In total, 11 patients and 73 segments exhibited positivity for LGE on CMR imaging. These were classified into three groups according to the segments: fibrotic segments (group I, n = 73), nonfibrotic segments in LGE-positive patients (group II, n = 103), and segments in LGE-negative patients (group III, n = 80). ECV- SECT, EEV- VPCT, myocardial blood flow (MBF), and myocardial blood volume (MBV) significantly differed among these groups (all P < 0.05). ECV- SECT was significantly higher and EEV- VPCT, MBF, and MBV were significantly lower in fibrotic myocardial segments than in nonfibrotic ones (all P < 0.01). ECV- SECT and EEV- VPCT independently affected myocardial fibrosis. There was no significant correlation between ECV- SECT and EEV- VPCT. The capability of EEV- VPCT to diagnose myocardial fibrosis was equivalent to that of ECV- SECT (area under the curve: 0.798 vs. 0.806, P = 0.844). ECV- SECT of > 41.2% and EEV- VPCT of < 10.3% indicated myocardial fibrosis. CONCLUSIONS: EEV- VPCT is actually first-pass distribution volume that can feasibly be used to quantify myocardial fibrosis. Furthermore, the diagnostic efficacy of EEV- VPCT is comparable to that of ECV- SECT.

Preliminary investigation of the effect of non-cardiac surgery on intraoperative islet and renal function: a single-center prospective cohort study.

Background: The effect of different non-cardiac surgical methods on islet and renal function remains unclear. We conducted a preliminary investigation to determine whether different surgical methods affect islet function or cause further damage to renal function. Methods: In this prospective cohort study, the clinical data of 63 adult patients who underwent non-cardiac surgery under general anesthesia were evaluated from February 2019 to January 2020. Patients were divided into the abdominal surgery group, the laparoscopic surgery group, and the breast cancer surgery group. The primary outcome was the difference between the effects of different surgical methods on renal function. Results: Islet and renal function were not significantly different between the groups. The correlation analysis showed that hematocrit (HCT) and hemoglobin (HB) were negatively correlated with fasting plasma glucose (FPG) (p < 0.05), MAP was positively correlated with C-peptide (p < 0.05), and HCT and Hb were positively correlated with serum creatinine (SCr) (p < 0.05). Fasting insulin (FINS) and C-peptide were negatively correlated with SCr (p < 0.05), and the homeostatic model assessment of insulin resistance (HOMA-IR) was positively correlated with SCr (p < 0.05). FINS, C-peptide, HOMA-IR, and the homeostatic model assessment of ß-cell function (HOMA-ß) were positively correlated with cystatin C (Cys C) (p < 0.05). Conclusion: FINS, C-peptide, and HOMA-IR had positive effects on beta-2-microglobulin (ß2-MG). FINS, C-peptide, and HOMA-IR were positively correlated with Cys C and ß2-Mg. While FINS and C-peptide were negatively correlated with SCr, HOMA-IR was positively correlated with SCr.

Joint associations among non-essential heavy metal mixtures and nutritional factors on glucose metabolism indexes in US adults: evidence from the NHANES 2011-2016.

Dietary intake can modify the impact of metals on human health, and is also closely related to glucose metabolism in human bodies. However, research on their interaction is limited. We used data based on 1738 adults aged ≥20 years from the National Health and Nutrition Examination Survey 2011-2016. We combined linear regression and restricted cubic splines with Bayesian kernel machine regression (BKMR) to identify metals associated with each glucose metabolism index (P < 0.05 and the posterior inclusion probabilities of BKMR >0.5) in eight non-essential heavy metals (barium, cadmium, antimony, tungsten, uranium, arsenic, lead, and thallium) and glucose metabolism indexes [fasting plasma glucose (FPG), blood hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)]. We identified two pairs of metals associated with glucose metabolism indexes: cadmium and tungsten to HbA1c and barium and thallium to HOMA-IR. Then, the cross-validated kernel ensemble (CVEK) approach was applied to identify the specific nutrient group (nutrients) that interacted with the association. By using the CVEK model, we identified significant interactions between the energy-adjusted diet inflammatory index (E-DII) and cadmium, tungsten and barium (all P < 0.05); macro-nutrients and cadmium, tungsten and barium (all P < 0.05); minerals and cadmium, tungsten, barium and thallium (all P < 0.05); and A vitamins and thallium (P = 0.043). Furthermore, a lower E-DII, a lower intake of carbohydrates and phosphorus, and a higher consumption of magnesium seem to attenuate the positive association between metals and glucose metabolism indexes. Our finding identifying the nutrients that interact with non-essential heavy metals could provide a feasible nutritional guideline for the general population to protect against the adverse effects of non-essential heavy metals on glucose metabolism.

Effect of ABT-639 on Cav3.2 channel activity and its analgesic actions in mouse models of inflammatory and neuropathic pain.

Cav3.2 T-type calcium channels are important targets for pain relief in rodent models of inflammatory and neuropathic pain. Even though many T-type channel blockers have been tested in mice, only one molecule, ABT-639, has been tested in phase II clinical studies and did not produce analgesic effects over placebo. Here we examined the effects of ABT-639 on Cav3.2 channel activity in tsA-201 cells and dorsal root ganglion (DRG) neurons, in comparison with another established Cav3.2 inhibitor Z944. These experiments revealed that Z944 mediated ∼100-fold more potent inhibition of Cav3.2 currents than ABT-639, with the latter blocking channel activity by less than 15 percent when applied at a concentration of 30 µM. A slight increase in ABT-639 potency was observed at more depolarized holding potentials, suggesting that this compound may act preferentially on inactivated channels. We tested the effects of both compounds in the Complete Freund's Adjuvant (CFA) model of chronic inflammatory pain, and in partial sciatic nerve injury model of neuropathic pain in mice. In the neuropathic pain model, both Z944 and ABT-639 reversed mechanical hypersensitivity to similar degrees when delivered systemically, but remarkably, when delivered intrathecally, only Z944 was effective. In the CFA model, both compounds reversed thermal hyperalgesia upon systemic delivery, but only Z944 mediated pain relief upon intrathecal delivery, indicating that ABT-639 acts primarily at peripheral sites. ABT-639 lost its analgesic effects in CFA treated Cav3.2 null mice, indicating that these channels are essential for ABT-639-mediated pain relief despite its poor inhibition of Cav3.2 currents.

Interaction Between Genetic Susceptibility and COVID-19 Pathogenesis in Pediatric Multisystem Inflammatory Disorders: The Role of Immune Responses.

Numerous studies have highlighted the emergence of coronavirus disease (COVID-19) symptoms reminiscent of Kawasaki disease in children, including fever, heightened multisystem inflammation, and multiorgan involvement, posing a life-threatening complication. Consequently, extensive research endeavors in pediatric have aimed to elucidate the intricate relationship between COVID-19 infection and the immune system. COVID-19 profoundly impacts immune cells, culminating in a cytokine storm that particularly inflicts damage on the pulmonary system. The gravity and vulnerability to COVID-19 are closely intertwined with the vigor of the immune response. In this context, the human leukocyte antigen (HLA) molecule assumes pivotal significance in shaping immune responses. Genetic scrutiny of HLA has unveiled the presence of at least one deleterious allele in children afflicted with multisystem inflammatory syndrome in children (MIS-C). Furthermore, research has demonstrated that COVID-19 exploits the angiotensin-converting enzyme 2 (ACE-2) receptor, transmembrane serine protease type 2, and various other genes to gain entry into host cells, with individuals harboring ACE-2 polymorphisms being at higher risk. Pediatric studies have employed diverse genetic methodologies, such as genome-wide association studies (GWAS) and whole exome sequencing, to scrutinize target genes. These investigations have pinpointed two specific genomic loci linked to the severity and susceptibility of COVID-19, with the HLA locus emerging as a notable risk factor. In this comprehensive review article, we endeavor to assess the available evidence and consolidate data, offering insights into current clinical practices and delineating avenues for future research. Our objective is to advance early diagnosis, stabilization, and appropriate management strategies to mitigate genetic susceptibility's impact on the incidence of COVID-19 in pediatric patients with multisystem inflammation.

Boosting the effectiveness of UV filters and sunscreen formulations using photostable, non-toxic inorganic platelets.

We have studied the size-dependent optical scattering of aqueous suspensions containing Mg2Al-LDH platelets, which exhibit high total- and side-scatterings. By incorporating 3 wt% Mg2Al-LDH platelets (280 nm) in a commercial sunscreen formulation, we achieved a twofold Sun Protection Factor boost, providing a promising, high-efficient and non-toxic strategy to enhance sunscreen effectiveness.

Deep learning system for true- and pseudo-invasion in colorectal polyps.

Over 15 million colonoscopies were performed yearly in North America, during which biopsies were taken for pathological examination to identify abnormalities. Distinguishing between true- and pseudo-invasion in colon polyps is critical in treatment planning. Surgical resection of the colon is often the treatment option for true invasion, whereas observation is recommended for pseudo-invasion. The task of identifying true- vs pseudo-invasion, however, could be highly challenging. There is no specialized software tool for this task, and no well-annotated dataset is available. In our work, we obtained (only) 150 whole-slide images (WSIs) from the London Health Science Centre. We built three deep neural networks representing different magnifications in WSIs, mimicking the workflow of pathologists. We also built an online tool for pathologists to annotate WSIs to train our deep neural networks. Results showed that our novel system classifies tissue types with 95.3% accuracy and differentiates true- and pseudo-invasions with 83.9% accuracy. The system's efficiency is comparable to an expert pathologist. Our system can also be easily adjusted to serve as a confirmatory or screening tool. Our system (available at http://ai4path.ca ) will lead to better, faster patient care and reduced healthcare costs.