HAIC Combined with lenvatinib plus PD-1 versus lenvatinib Plus PD-1 in patients with high-risk advanced HCC: a real-world study.

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.

Identification of benzo[b]thiophene-1,1-dioxide derivatives as novel PHGDH covalent inhibitors.

The increased de novo serine biosynthesis confers many advantages for tumorigenesis and metastasis. Phosphoglycerate dehydrogenase (PHGDH), a rate-limiting enzyme in serine biogenesis, exhibits hyperactivity across multiple tumors and emerges as a promising target for cancer treatment. Through screening our in-house compound library, we identified compound Stattic as a potent PHGDH inhibitor (IC50 = 1.98 ± 0.66 µM). Subsequent exploration in structural activity relationships led to the discovery of compound B12 that demonstrated the increased enzymatic inhibitory activity (IC50 = 0.29 ± 0.02 µM). Furthermore, B12 exhibited robust inhibitory effects on the proliferation of MDA-MB-468, NCI-H1975, HT1080 and PC9 cells that overexpress PHGDH. Additionally, using a [U-13C6]-glucose tracing assay, B12 was found to reduce the production of glucose-derived serine in MDA-MB-468 cells. Finally, mass spectrometry-based peptide profiling, mutagenesis experiment and molecular docking study collectively suggested that B12 formed a covalent bond with Cys421 of PHGDH.

Age-dependent associations between RSA reactivity, affective and cognitive regulation, and psychopathology risk in young children exposed to varying levels of socioeconomic disadvantage.

This study examined autonomic nervous system activity (respiratory sinus arrhythmia [RSA]) as a biomarker of psychopathology in an ethnically and socioeconomically diverse sample (N = 57) of young children ages 4-7 years. RSA was measured at baseline and across four standardized tasks designed to assess self-regulation in both affective (i.e., "hot") and cognitive (i.e., "cool") contexts during early childhood. Our findings reveal that age moderated RSA activity, such that reduced RSA suppression was associated with a heightened risk of externalizing problems among older children during "cool" and "hot" contexts; for younger children, only RSA suppression during "hot" contexts predicted externalizing risk. The influence of socioeconomic disadvantage did not moderate the relationship between RSA and the risk of psychopathology, and there were minimal associations between RSA suppression and internalizing symptoms at this age range. These results suggest that autonomic variability may be a more effective predictor of psychopathology risk in older children, perhaps as they transition into formal schooling and face increasingly complex cognitive and social demands. Findings have implications for the identification of psychopathology in early developmental periods when regulation over emotions becomes essential for academic and social success.

Moderate increase of precipitation stimulates CO2 production by regulating soil organic carbon in a saltmarsh.

Saltmarsh is widely recognized as a blue carbon ecosystem with great carbon storage potential. Yet soil respiration with a major contributor of atmospheric CO2 can offset its carbon sink function. Up to date, mechanisms ruling CO2 emissions from saltmarsh soil remain unclear. In particular, the effect of precipitation on soil CO2 emissions is unclear in coastal wetlands, due the lack of outdoor data in real situations. We conducted a 7-year field manipulation experiment in a saltmarsh in the Yellow River Delta, China. Soil respiration in five treatments (-60%, -40%, +0%, +40%, and + 60% of precipitation) was measured in the field. Topsoils from the last 3 years (2019-2021) were analyzed for CO2 production potential by microcosm experiments. Furthermore, quality and quantity of soil organic carbon and microbial function were tested. Results show that only the moderate precipitation rise of +40% induced a 66.2% increase of CO2 production potential for the microcosm experiments, whereas other data showed a weak impact. Consistently, soil respiration was also found to be strongest at +40%. The CO2 production potential is positively correlated with soil organic carbon, including carbon quantity and quality. But microbial diversity did not show any positive response to precipitation sizes. r-/K-strategy seemed to be a plausible explanation for biological factors. Overall, our finding reveal that a moderate precipitation increase, not decrease or a robust increase, in a saltmarsh is likely to improve soil organic carbon quality and quantity, and bacterial oligotroph:copiotroph ratio, ultimately leading to an enhanced CO2 production.

Discovery of Dual Function Agents That Exhibit Anticancer Activity via Catastrophic Nicotinamide Adenine Dinucleotide Depletion.

Nicotinamide adenine dinucleotide (NAD) is essentially involved in many biological processes of cancer cells, yet chemical intervention of NAD biosynthesis failed to obtain an optimal therapeutic benefit. We herein developed a new strategy to induce catastrophic NAD depletion by concurrently impairing NAD synthesis and promoting NAD consumption. We designed a series of new compounds that conjugate an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in the NAD salvage pathway, with a DNA-alkylating agent. Among them, compound 11b exhibited potent anticancer efficacy in cancer cell lines and mouse tumor models with intrinsic resistance to the parent compound FK866 or chlorambucil. Compound 11b caused catastrophic NAD depletion via a synergistic effect between the NAD salvage pathway blockade and DNA damage-triggered NAD consumption. Our findings suggest a new intervention strategy for causing catastrophic NAD depletion in cancer cells and provide basis for the development of new inhibitors targeting NAD metabolism.

Genetic characterization of a Salmonella enterica serovar Typhimurium isolated from an infant with concurrent resistance to ceftriaxone, ciprofloxacin and azithromycin.

OBJECTIVES: To investigate the resistance mechanism of a Salmonella Typhimurium (S. Typhimurium) isolated from a faecal sample of an infant, which exhibited concurrent resistance to ceftriaxone, ciprofloxacin and azithromycin. METHODS: Antimicrobial susceptibility testing was performed by broth microdilution in two kinds of drug-sensitive plates. Antimicrobial resistance (AMR) genes were identified by whole genome sequencing and bioinformatics analysis. Genotyping of the strain was performed by multilocus sequence typing (MLST). Plasmid DNA was sequenced and analysed using plasmid bioinformatics tools. RESULTS: The SH11G993 strain was resistant to 28 antibiotics and carried 54 AMR genes. MLST results showed that the strain belonged to a rare genotype. The plasmid profile and plasmid sequencing showed that the strain carried two resistance plasmids. The pSH11G993-1 carried 14 AMR genes (especially co-harboured blaCMY-2, mphA and ermB) and a variety of insertion sequences, belonging to the IncC. The pSH11G993-2 carried 3 AMR genes and 9 virulence genes, belonging to the IncFIB-FII, forming a novel resistance and virulence co-harbouring plasmid. CONCLUSIONS: Our findings highlight that continuously monitor the changes in antibiotic resistance patterns and research on the resistance mechanisms in potential human pathogens are imperative.

Efficacy of TACE Combined with Lenvatinib Plus Sintilimab for Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava and/or Right Atrium.

Purpose: To validate the safety and effectiveness of transarterial chemoembolization (TACE) combination with lenvatinib and sintilimab in treating hepatocellular carcinoma (HCC) patients with inferior vena cava (IVC) and/or right atrium (RA) tumor thrombosis (TT). Methods: This study retrospectively analyzed HCC patients with IVC and/or RA TT treated with TACE combined with lenvatinib plus sintilimab. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the anti-tumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results: A total of 58 patients were screened for eligibility between March 2019 and May 2022. At the time of data collection, 48.2% of patients were still receiving treatment. The median follow-up was 23.5 months. The ORR was 48.3%, the DCR was 91.4%, the median OS was 17.3 months, and the median PFS was 13.0 months. The ORR for IVC/RA TT was 62.1%, DCR was 94.9%, and the median PFS was 14.3 months. 56.9% of patients experienced ≥ grade 3 TRAEs, such as hypertension (10.3%) and elevated liver enzymes (13.8%). No new safety signals were identified. Participants with low levels of serum PCT value had satisfactory prognoses. Conclusion: TACE combination with lenvatinib plus sintilimab is effective in treating HCC with IVC and/or RA TT. The toxicities were manageable, with no unexpected safety signals. The baseline levels of serum PCT might be the predictive biomarkers for the triple combination therapy.

Hepatic Arterial Infusion Chemotherapy Combined with Lenvatinib Plus Humanized Programmed Death Receptor-1 in Patients with High-Risk Advanced Hepatocellular Carcinoma: A Real-World Study.

Purpose: The treatment of hepatocellular carcinoma (HCC) patients with high-risk features (Vp4, and/or tumor occupancy≥50%) has not been standardized and has poor outcomes. The present study aimed to assess the safety, efficacy, and prognostic impact of lenvatinib, hepatic arterial infusion chemotherapy (HAIC), and humanized programmed death receptor-1 (PD-1) in treating high-risk patients and to explore the biomarkers that may predict the efficacy. Methods: HCC patients with high-risk features treated with lenvatinib, HAIC, and PD-1 were analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the antitumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. Results: Between February 2020 and July 2022, 97 patients were enrolled in this retrospective cohort study. The median follow-up time was 447 days. During analysis, 65 patients had disease progression, and 39 patients died. The median PFS and OS were 295 and 579 days, respectively. According to RECIST 1.1 and mRECIST, the ORR was 64.9% and 78.3%, respectively, and the DCR was 92.8%. The median and intrahepatic DOR was 363 and 462 days, respectively. Treatment-related grade 3 or 4 adverse events occurred in 64 (65.9%) patients, and the most common adverse events were hypertension (9.3%), thrombocytopenia (7.2%), and elevated aspartate transaminase (7.2%). Participants with low levels of serum procalcitonin (PCT) had satisfactory prognosis. Conclusion: Lenvatinib, HAIC, and PD-1 were safe and showed promising antitumor activity against HCC with high-risk features. The initial levels of procalcitonin might be the predictive biomarkers for the combined treatment.

Analysis of visual quality after multifocal intraocular lens implantation in post-LASIK cataract patients.

With the development of refractive corneal surgery, excimer laser in situ keratomileusis (LASIK) has become a common refractive surgery procedure. However, post-LASIK patients are at increased risk of developing cataracts as they age and often require IOL implantation. The choice of IOLs is particularly important for these patients, who have smaller residual refractive error and have higher requirements for post-cataract vision recovery and visual quality than the general population. Multifocal IOLs are widely used in clinical practice for patients with high visual acuity needs, such as cataract patients after refractive keratomileusis, due to their advantages of providing excellent near and distance visual acuity; however, compared to monofocal IOLs, multifocal IOLs can lead to postoperative problems related to visual quality such as increased higher order aberrations and decreased contrast sensitivity. Therefore, whether multifocal IOLs have advantages for post-LASIK cataract patients, such as improving the visual quality of such patients, has attracted attention. In this paper, we analyze the current status of research on the implantation of multifocal IOLs in post-LASIK cataract patients by domestic and foreign experts, review and summarize the relevant literature, and propose further discussion in the context of the actual situation of postoperative visual quality and vision recovery.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Ambient precipitation determines the sensitivity of soil respiration to precipitation treatments in a marsh.

The effects in field manipulation experiments are strongly influenced by amplified interannual variation in ambient climate as the experimental duration increases. Soil respiration (SR), as an important part of the carbon cycle in terrestrial ecosystems, is sensitive to climate changes such as temperature and precipitation changes. A growing body of evidence has indicated that ambient climate affects the temperature sensitivity of SR, which benchmarks the strength of terrestrial soil carbon-climate feedbacks. However, whether SR sensitivity to precipitation changes is influenced by ambient climate is still not clear. In addition, the mechanism driving the above phenomenon is still poorly understood. Here, a long-term field manipulation experiment with five precipitation treatments (-60%, -40%, +0%, +40%, and +60% of annual precipitation) was conducted in a marsh in the Yellow River Delta, China, which is sensitive to soil drying-wetting cycle caused by precipitation changes. Results showed that SR increased exponentially along the experimental precipitation gradient each year and the sensitivity of SR (standardized by per 100 mm change in precipitation under precipitation treatments) exhibited significant interannual variation from 2016 to 2021. In addition, temperature, net radiation, and ambient precipitation all exhibited dramatic interannual variability; however, only ambient precipitation had a significant negative correlation with SR sensitivity. Moreover, the sensitivity of SR was significantly positively related to the sensitivity of belowground biomass (BGB) across 6 years. Structural equation modeling and regression analysis also showed that precipitation treatments significantly affected SR and its autotrophic and heterotrophic components by altering BGB. Our study demonstrated that ambient precipitation determines the sensitivity of SR to precipitation treatments in marshes. The findings underscore the importance of ambient climate in regulating ecosystem responses in long-term field manipulation experiments.

The sustainability of urbanized land: Impacts of the growth of urbanized land in prefecture-level cities in China.

The sustainability of land conversion to urban use is an important factor that promotes sustainable urbanization. However, China's local governments have relied too much on the land finance model for urbanization, which has led to disordered growth of urban land, ultimately posing a threat to ecosystem security and socioeconomic development. Effectively evaluating the factors that influence the growth of urban land is critical to improving the sustainability of urban land use. In this study, we explored the factors that affect the growth in the area of urban land using spatial analysis models based on panel data for Chinese prefecture-level cities from 2007 to 2019. We found that fiscal decentralization, infrastructure, industrialization, and industrial upgrading were the main factors responsible for the growth of urban land, but that their degrees of influence differed between regions. Our findings identify the necessity for local governments to design urban land-use policies and perform strategic planning for urban land use to improve sustainability based on the main factors that influenced the growth of urban land in each region.

Immunogenicity, safety and consistency of seven lots of an inactivated COVID-19 vaccine in healthy children and adolescents: a randomized, double-blind, controlled, phase IV clinical trial.

Background: CoronaVac has been authorized worldwide for preventing coronavirus disease 2019. Information on the safety, immunogenicity and consistency of different lots and workshops of CoronaVac is presented here. Methods: In this randomized, double-blind, phase IV clinical trial in healthy children and adolescents aged 3-17 years, we aimed to assess the lot-to-lot and workshop-to-workshop consistency, as well as immunogenicity and safety of seven lots of commercial-scale CoronaVac from three workshops. Eligible participants were enrolled into three age cohorts (3-5, 6-11 and 12-17 years). Within each cohort, participants were randomly assigned to seven groups to receive two doses of CoronaVac, with four weeks apart. Serum samples were collected before the first dose and 28 days after the second dose for neutralizing antibody testing. The primary objective was to evaluate the consistency of immune response among different lots within workshop 2 or 3, as well as among different workshops. The primary endpoint was geometric mean titer (GMT) of neutralizing antibody at 28 days after full-course vaccination. Results: Between July 27th and November 19th, 2021, a total of 2,520 eligible participants were enrolled. Results showed that 95% confidence intervals (CIs) of GMT ratios for all comparative groups among different lots or workshops were within the equivalence criteria of [0.67, 1.5]. The GMT and seroconversion rate for all participants were 126.42 (95%CI: 121.82, 131.19) and 99.86% (95%CI: 99.59%, 99.97%) at 28 days after two-dose vaccination. The incidences of adverse reactions were similar among seven lots, and most adverse reactions were mild in Grade 1, with no serious adverse event. Conclusion: CoronaVac is well-tolerated and can elicit a good immune response among children and adolescents. Lot-to-lot consistency results indicate stable manufacturing of commercial-scale CoronaVac.

[Effects of simulated precipitation changes on plant community characteristics of wetland in the Yellow River Delta, China]. / 模拟降雨量变化对黄河三角洲湿地植物群落特征的影响.

Under the changing climate scenario, changes in precipitation regimes are expected to alter soil water and salinity conditions, with consequences on the characteristics of plant community in estuarine wetland. Here, we used a six-year (2015-2020) precipitation manipulation experiment to examine how plant community characteristics responded to precipitation changes in the Yellow River Delta. The results showed that soil electrical conductivity significantly decreased, while soil moisture significantly increased with increasing precipitation. Precipitation changes altered plant community composition. Increased precipitation reduced the absolute dominance of Suaeda glauca and Suaeda salsa, but increased that of Triarrhena sacchariflora and Imperata cylindrica. Shannon index and Margalef richness index of plant community significantly increased with increasing precipitation. Compared with the control, both decreased and increased precipitation decreased the plant community abundance, frequency and coverage. The treatment of 60% increased precipitation significantly decreased plant community frequency by 54.9%, while the 60% decreased precipitation, 40% decreased precipitation, 40% increased precipitation and 60% increased precipitation treatment significantly decreased plant abundance by 38.9%, 33.8%, 35.8% and 45.7%, respectively. The aboveground biomass significantly increased with increasing precipitation, but aboveground plant biomass under 60% increased precipitation treatment being lower than that reducing under 40% increased precipitation treatment, probably due to the negative effects of flooding stress. In addition, Margalef richness index had a significantly positive relationship with aboveground biomass. Aboveground biomass, Shannon diversity index, Margalef richness index, and Simpson diversity index were negatively related to soil electrical conductivity, and aboveground plant biomass was positively related to soil moisture. Our results revealed that precipitation changes regulate growth characteristics, species composition, and diversity of plant community by altering soil water and salinity conditions in a coastal wetland.

Corrigendum: A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

[This corrects the article DOI: 10.3389/fmicb.2021.779749.].

Optimal Initial Time Point of Local Radiotherapy for Unresectable Lung Adenocarcinoma: A Retrospective Analysis on Overall Arrangement of Local Radiotherapy in Advanced Lung Adenocarcinoma.

Local radiotherapy (LRT) is reported to be of survival benefit for advanced non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. This IRB-approved retrospective analysis identified patients diagnosed with stage IIIb-IV unresectable lung adenocarcinoma who initiated front-line LRT at our institution between 2017 and 2020. The receiver operating characteristic (ROC) curve analyses were used to cut off the initial time of LRT (before and beyond 53 days). Patients were divided into two groups: one early to initiate radiotherapy group (≤53 days, EAR group) and one deferred radiotherapy group (>53 days, DEF group). The Kaplan-Meier method was used to estimate time-to-event endpoints; the Cox proportional hazard model was used to find out predictors of progression-free survival (PFS) and overall survival (OS). A total of 265 patients with a median age of 57 were enrolled. The median follow-up time was 26.4 months (ranging from 2.2 to 69.7 months). The mOS was 38.6 months and mPFS was 12.7 months. Age >60, bone and brain metastases, multisite metastases, and EGFR 19 mutation were independent predictors associated with OS. Early initiation of local radiotherapy within 53 days after diagnosis resulted in better PFS, but not in OS. A better OS was observed in patients with bone metastasis who underwent local radiotherapy initiated within 53 days.

A Severe Gastroenteritis Outbreak of Salmonella enterica Serovar Enteritidis Linked to Contaminated Egg Fried Rice, China, 2021.

Salmonella contamination of eggs and egg shells has been identified as a public health problem worldwide. Here, we reported an outbreak of severe gastrointestinal symptoms caused by Salmonella enterica serovar Enteritidis (S. enteritidis) in China. We evaluated the outbreak by using epidemiological surveys, routine laboratory testing methods, and whole genome sequencing (WGS). This outbreak occurred in a canteen in Beijing, during March 9-11, 2021, 225 of the 324 diners who have eaten at the canteen showed gastrointestinal symptoms. The outbreak had characteristical epidemiological and clinical features. It caused a very high attack rate (69.4%) in a short incubation time. All patients developed diarrhea and high fever, accompanied by abdominal pain (62.3%), nausea (50.4%), and vomiting (62.7%). The average frequency of diarrhea was 12.4 times/day, and the highest frequency of diarrhea was as high as 50 times/day. The average fever temperature was 39.4°C, and the highest fever temperature was 42°C. Twenty strains of S. enteritidis were recovered, including 19 from the patients samples, and one from remained egg fried rice. Antibiotic susceptibility test showed that the 20 outbreak strains all had the same resistance pattern. PFGE results demonstrated that all 20 strains bore completely identical bands. Phylogenetic analysis based on WGS revealed that all 20 outbreak strains were tightly clustered together. So the pathogenic source of this food poisoning incident may was contaminated egg fried rice. Resistance gene analysis showed that the outbreak strains are all multi-drug resistant strains. Virulence gene analysis indicated that these outbreak strains carried a large number of virulence genes, including 2 types of Salmonella pathogenicity islands (SPI-1 and SPI-2). Other important virulence genes were also carried by the outbreak strains, such as pefABCD, rck and shdA. And the shdA gene was not in other strains located in the same evolutionary branch as the outbreak strain. We speculated that this is a significant reason for the serious symptoms of gastroenteritis in this outbreak. This outbreak caused by S. enteritidis suggested government should strengthen monitoring of the prevalence of outbreak clone strains, and take measures to mitigate the public health threat posed by contaminated eggs.

Investigating Language and Domain-General Processing in Neurotypicals and Individuals With Aphasia - A Functional Near-Infrared Spectroscopy Pilot Study.

Brain reorganization patterns associated with language recovery after stroke have long been debated. Studying mechanisms of spontaneous and treatment-induced language recovery in post-stroke aphasia requires a network-based approach given the potential for recruitment of perilesional left hemisphere language regions, homologous right hemisphere language regions, and/or spared bilateral domain-general regions. Recent hardware, software, and methodological advances in functional near-infrared spectroscopy (fNIRS) make it well-suited to examine this question. fNIRS is cost-effective with minimal contraindications, making it a robust option to monitor treatment-related brain activation changes over time. Establishing clear activation patterns in neurotypical adults during language and domain-general cognitive processes via fNIRS is an important first step. Some fNIRS studies have investigated key language processes in healthy adults, yet findings are challenging to interpret in the context of methodological limitations. This pilot study used fNIRS to capture brain activation during language and domain-general processing in neurotypicals and individuals with aphasia. These findings will serve as a reference when interpreting treatment-related changes in brain activation patterns in post-stroke aphasia in the future. Twenty-four young healthy controls, seventeen older healthy controls, and six individuals with left hemisphere stroke-induced aphasia completed two language tasks (i.e., semantic feature, picture naming) and one domain-general cognitive task (i.e., arithmetic) twice during fNIRS. The probe covered bilateral frontal, parietal, and temporal lobes and included short-separation detectors for scalp signal nuisance regression. Younger and older healthy controls activated core language regions during semantic feature processing (e.g., left inferior frontal gyrus pars opercularis) and lexical retrieval (e.g., left inferior frontal gyrus pars triangularis) and domain-general regions (e.g., bilateral middle frontal gyri) during hard versus easy arithmetic as expected. Consistent with theories of post-stroke language recovery, individuals with aphasia activated areas outside the traditional networks: left superior frontal gyrus and left supramarginal gyrus during semantic feature judgment; left superior frontal gyrus and right precentral gyrus during picture naming; and left inferior frontal gyrus pars opercularis during arithmetic processing. The preliminary findings in the stroke group highlight the utility of using fNIRS to study language and domain-general processing in aphasia.

Links between socioeconomic disadvantage, neural function, and working memory in early childhood.

Children reared in socioeconomically disadvantaged environments are at risk for academic, cognitive, and behavioral problems. Mounting evidence suggests that childhood adversities, encountered at disproportionate rates in contexts of socioeconomic risk, shape the developing brain in ways that explain disparities. Circuitries that subserve neurocognitive functions related to memory, attention, and cognitive control are especially affected. However, most work showing altered neural function has focused on middle childhood and adolescence. Understanding alterations in brain development during foundational points in early childhood is a key next step. To address this gap, we examined functional near-infrared-spectroscopy-based neural activation during a working memory (WM) task in young children aged 4-7 years (N = 30) who varied in socioeconomic risk exposure. Children who experienced greater disadvantage (lower income to needs ratio and lower Hollingshead index) exhibited lower activation in the lateral prefrontal cortex than children who experienced less to no disadvantage. Variability in prefrontal cortex activation, but not behavioral performance on the WM task, was associated with worse executive functioning in children as reported by parents. These findings add to existing evidence that exposure to early adversity, such as socioeconomic risk, may lead to foundational changes in the developing brain, which increases risk for disparities in functioning across multiple cognitive and social domains.