A chromosome-level genome assembly of the legume pod borer, Maruca vitrata Fabricius (Lepidoptera: Crambidae).

Maruca vitrata, a significant pest of legumes, impacts food security in Asia and Africa. This study presents a high-quality genome assembly of M. vitrata, utilizing advanced sequencing technologies including Nanopore long-read, MGI short-read, and Hi-C. The genome, totaling 482.3 Mb with a contig N50 of 2.91 Mb, features 41.58% repetitive sequences and encompasses 13,320 protein-coding genes. We performed comparative genomic analyses to affirm the accuracy and completeness of the protein sequences assembled, ensuring the assembly's integrity. Additionally, the annotation of 83 Cytochrome P450 (CYP) genes further confirms the comprehensive nature of the genome assembly and its annotations. This genome assembly not only deepens our understanding of M. vitrata biology but also supports the development of sustainable pest management strategies. This research highlights the importance of genomics in advancing sustainable agricultural solutions through innovative pest management approaches.

Characteristics of Endemic Mycoses Talaromyces marneffei Infection Associated with Inborn Errors of Immunity.

BACKGROUND: Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that causes endemic mycoses, which could lead to multiple organ damage. Talaromycosis is frequently disregarded as an early cautionary sign of immune system disorders in non-HIV-infected children. OBJECTIVE: We conduct a comprehensive review of the genotypes and clinical features of talaromycosis in patients with IEI to enhance clinical awareness regarding T. marneffei as a potential opportunistic pathogen in individuals with immune deficiencies. METHODS: A systematic literature review was performed by searching PubMed, Cochrane Central Register of Controlled Trials, Web of Science, EMBASE, and Scopus. Data on IEI patients with talaromycosis, including genotypes and their immunological and clinical features, were collected. RESULTS: Fifty patients with talaromycosis and IEI were included: XHIM (30.0%), STAT3-LOF deficiency (20.0%), STAT1-GOF (20.0%), IL2RG (6.00%), IFNGR1 (6.0%), IL12RB1 (4.0%), CARD9 (4.0%), COPA (4.0%), ADA (2.0%), RELB deficiency (2.0%), and NFKB2 (2.0%). Common symptoms of respiratory (43/50, 86.0%), skin (17/50, 34.0%), lymph node (31/50, 62.0%), digestive (34/50, 68.0%), and hematologic (22/50, 44.0%) systems were involved. The CT findings of the lungs may include lymph node calcification (9/30), interstitial lesions (8/30), pulmonary cavities (8/30), or specific pathogens (4/30), which could be easily misdiagnosed as tuberculosis infection. Amphotericin B (26/43), Voriconazole (24/43) and Itraconazole (22/43) were used for induction therapy. Ten patients were treated with Itraconazole sequentially and prophylaxis. 68.0% (34/50) of patients were still alive, and 4.0% (2/50) of were lost to follow-up. The disseminated T. marneffei infection resulted in the deaths of 14 individuals. CONCLUSIONS: The XHIM, STAT1-GOF, and STAT3-LOF demonstrated the highest susceptibility to talaromycosis, indicating the potential involvement of cellular immunity, IL-17 signaling, and the IL-12/IFN-γ axis in T. marneffei defense. T. marneffei infection may serve as an early warning indicator of IEI. For IEI patients suspected of T. marneffei, metagenomic next-generation sequencing (mNGS) could rapidly and effectively identify the causative pathogen. Prompt initiation of antifungal therapy is crucial for optimizing patient outcomes.

Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial.

OBJECTIVES: Given the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA. METHOD: In this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12. RESULTS: Sixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%-95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred. CONCLUSION: This is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.

Fruit ripening and postharvest changes in very early-harvested tomatoes.

It is well known that if a fruit is harvested extremely early its development and function are interrupted, and it may never attain full maturity and optimal quality. Reports revealing insights regarding the alterations of maturation, ripening and postharvest quality in very early picked fruits are rare. We examined the effects of early harvesting on tomatoes by characterizing different accessions at the molecular, physiological, and biochemical levels. We found that even very early-harvested fruits could achieve postharvest maturation and ripening though with some defects in pigment and cuticle formation, and seeds from very early-harvested fruits could still germinate and develop as normal and healthy plants. One critical regulator of tomato cuticle integrity, SlCER1-2, was shown to contribute to cuticle defects in very early-harvested fruits. Very early fruit harvest still allowing ripening and seed development indicate that the genetic and physiological programs of later maturation and ripening are set into motion early in fruit development and are not dependent on complete fruit expansion nor attachment to the plant.

Clinical and genetic analysis of macrophage activation syndrome complicating juvenile idiopathic inflammatory myopathies.

BACKGROUND: Macrophage activation syndrome (MAS) is a serve complication of juvenile idiopathic inflammatory myopathies (JIIMs). This study delineates the clinical manifestations and genetic underpinnings of JIIM-MAS patients. METHODS: We retrospectively analysed clinical and UNC13D gene from JIIM patients admitted to our centre between 2011 and 2021 to identify cases of MAS. Additionally, a literature review summarising reported cases of JIIMs and MAS was performed. RESULTS: Of 773 JIIM patients, 10 (1.3%) were diagnosed with MAS. All patients presented with persistent fever and hyperferritinaemia. Seventy percent of patients met the HLH-2004 criteria, while 90% met the 2016 sJIA-MAS criteria. Most patients received combined treatment of corticosteroids and immunosuppressants. UNC13D gene analysis was performed in six patients. A homozygous pathogenic mutation (c.2588G>A) was detected in one patient with recurrent MAS, and twenty-eight single-nucleotide polymorphisms (SNPs) were detected. Eighty percent of patients exhibiting a consistent combination of ten SNPs compared to JIIM patients without MAS (35%). CONCLUSION: MAS is an early and often overlooked complication of JIIMs. The 2016 sJIA-MAS criteria may facilitate early diagnosis. Combined corticosteroid and immunosuppressant therapy prove effective. An increased prevalence of UNC13D gene polymorphisms was observed in JIIM-MAS patients, highlighting the necessity for further investigations. IMPACT: This study aimed to delineate the clinical manifestations and genetic underpinnings of macrophage activation syndrome (MAS) in ten patients with juvenile idiopathic inflammatory myopathies (JIIMs). MAS has been recognised as a complication of JIIMs. However, only a few case reports provide comprehensive descriptions of MAS in JIIM patients, and there are few reports related to UNC13D mutations in these patients. This article offers single-centre clinical insights to enhance the identification and management of MAS in JIIM patients, while also highlighting the potential association between MAS occurrence and UNC13D gene polymorphisms.

Clinical characteristics, effectiveness and cost of different treatment methods for invasive Klebsiella pneumoniae liver abscess syndrome. / ä¾µè¢­æ€§è‚ºç‚Žå ‹é›·ä¼¯èŒè‚è„“è‚¿ç»¼åˆå¾çš„ä¸´åºŠç‰¹å¾åŠä¸åŒæ²»ç–—æ–¹å¼çš„æœ‰æ•ˆæ€§ä¸Žè´¹ç”¨åˆ†æž.

OBJECTIVES: Bacterial liver abscess is one of the common infectious diseases of the digestive system. Invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS) refers to cases where, in addition to liver abscess, there are migratory infections foci or other invasive manifestations. The clinical characteristics and risk factors of IKLAS are not fully elucidated, and there is a lack of research on the effectiveness and cost-effectiveness of different treatment methods. This study aims to compare the clinical characteristics of patients with IKLAS and non-IKLAS, and explore effective and economical treatment methods. METHODS: This retrospective study collected medical records of patients with Klebsiella pneumoniae liver abscess treated at Xiangya Hospital of Central South University from January 2010 to December 2023. A total of 201 patients were included, dividing into an IKLAS group (n=37) and a non-IKLAS group (n=164). Differences in demographics, symptoms and signs, laboratory indicators, imaging characteristics, comorbidities, treatment methods, treatment outcomes, and direct treatment costs between 2 groups were analyzed. The study also compared the effectiveness and costs of different treatment methods. RESULTS: Compared with the non-IKLAS group, the proportion of patients with diabetes, Quick Sequential Organ Failure Assessment (qSOFA)≥2, immune deficiency, anemia, and thrombocytopenia in the IKLAS group was higher, and the level of procalcitonin at the onset in the IKLAS group was also higher (all P<0.05). In terms of symptoms and signs, the IKLAS group had a higher proportion of visual abnormalities and a lower proportion of complaints of abdominal pain (both P<0.05). In terms of complications, the incidence of combined pleural effusion, pulmonary infection, acute renal failure, respiratory failure, and multiple organ failure was higher in the IKLAS group (all P<0.05). The IKLAS group had a higher proportion of patients treated with antibiotics alone (24.32% vs 11.59%), while the non-IKLAS group had a higher proportion of patients treated with antibiotics combined with puncture and drainage (86.59% vs 64.86%, both P<0.05). The overall effective rate of the IKLAS group (83.78%) was lower than that of the non-IKLAS group (95.73%), and the treatment and drug costs were higher (all P<0.05). The treatment method of antibiotics combined with surgical resection of infectious foci showed a 100% improvement rate, antibiotics combined with abscess puncture and drainage had an 84.9% improvement rate, and in antibiotics alone had an 82.1% improvement rate, with statistical differences among the 3 treatment methods (P<0.05). In terms of treatment costs, antibiotics alone were the most expensive (P<0.05). CONCLUSIONS: Patients with IKLAS have poorer prognosis and higher direct medical costs. The combination of abscess puncture and drainage or surgery has a higher improvement rate and lower hospitalization costs compared to antibiotics alone, suggesting that surgical intervention may reduce antibiotic costs and save medical expenses.

Desmodium intortum (Mill.) Urb. Protein Isolate Aggregates as Pickering Stabilizers: Physicochemical Characteristics and Emulsifying Properties.

This work aimed to investigate the feasibility of fabricating Pickering emulsions stabilized by Desmodium intortum protein isolate (DIPI) aggregates. The DIPI aggregates were formed using heat treatment, and the effects of ionic strength and pH on their properties were investigated. The heat-treated protein exposes its hydrophobic groups due to structural damage, resulting in rapid aggregation of the protein into aggregates with a size of 236 nm. The results showed that the aggregates induced by ionic strength had larger particle size and higher surface hydrophobicity and partial wettability. Moreover, this study explored effective strategies for bolstering Pickering emulsion stability through optimized DIPI aggregate concentration (c) and oil fraction (ø). The DIPI Pickering emulsion (DIPIPE) formed at c = 5% and ø = 0.7 was still highly stable after 30 days of storage. As confirmed by laser confocal microscopy, DIPI aggregates could be adsorbed onto the oil-water interface to form a network structure that could trap oil droplets in the network. Collectively, the Pickering emulsion stabilized by DIPI aggregates exhibited excellent stability, which not only deeply utilizes the low-value protein resources in the Desmodium intortum for the first time, but also demonstrates the potential of DIPI for the bio-based field.

A single-centre study on abnormal antinuclear antibodies in children caused by intravenous infusion of gamma globulin.

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children. Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group. Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results. Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies.

Chromosome-level genome assembly and annotation of the Rhabdophis nuchalis (Hubei keelback).

Rhabdophis nuchalis, a snake widely distributed in China, possesses a unique trait: glands beneath the skin on its neck and back, known as nucho-dorsal glands. These features make it a valuable subject for studying genetic diversity and the evolution of complex traits. In this study, we obtained a high-quality chromosome-level reference genome of R. nuchalis using MGI short-read sequencing, PacBio Revio long-read sequencing, and Hi-C sequencing techniques. The final assembly comprised 1.92 Gb of the R. nuchalis genome, anchored to 20 chromosomes (including 9 macrochromosomes and 11 microchromosomes), with a contig N50 of 104.79 Mb, a scaffold N50 of 204.96 Mb, and a BUSCO completeness of 97.50%. Additionally, we annotated a total of 1.09 Gb of repetitive sequences (which constitute 56.51% of the entire genome) and identified 22,057 protein-coding genes. This high-quality reference genome of R. nuchalis furnishes essential genomic data for comprehending the genetic diversity and evolutionary history of the species, as well as for facilitating species conservation efforts and comparative genomics studies.

Related type 2C protein phosphatases Pic3 and Pic12 negatively regulate immunity in tomato to Pseudomonas syringae.

Type 2C protein phosphatases (PP2Cs) constitute a large family in most plant species but relatively few of them have been implicated in immunity. To identify and characterize PP2C phosphatases that affect tomato (Solanum lycopersicum) immunity, we used CRISPR/Cas9 to generate loss-of-function mutations in 11 PP2C-encoding genes whose expression is altered in response to immune elicitors or pathogens. We report that two closely related PP2C phosphatases, Pic3 (PP2C immunity-associated candidate 3) and Pic12, are involved in regulating resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst). Loss-of-function mutations in Pic3 led to enhanced resistance to Pst in older but not younger leaves, whereas such mutations in Pic12 resulted in enhanced resistance in both older and younger leaves. Overexpression of Pic3 and Pic12 proteins in leaves of Nicotiana benthamiana inhibited resistance to Pst, and this effect was dependent on Pic3/12 phosphatase activity and an N-terminal palmitoylation motif associated with localization to the cell periphery. Pic3, but not Pic12, had a slight negative effect on flagellin-associated reactive oxygen species generation, although their involvement in the response to Pst appeared independent of flagellin. RNA-sequencing analysis of Rio Grande (RG)-PtoR wild-type plants and two independent RG-pic3 mutants revealed that the enhanced disease resistance in RG-pic3 older leaves is associated with increased transcript abundance of multiple defense related genes. RG-pic3/RG-pic12 double mutant plants exhibited stronger disease resistance than RG-pic3 or RG-pic12 single mutants. Together, our results reveal that Pic3 and Pic12 negatively regulate tomato immunity in an additive manner through flagellin-independent pathways.

Isolated distal deep vein thrombosis associated with adenomyosis: Case report and literature review.

While adenomyosis is commonly associated with a mild risk of thrombotic complications, the presence of additional thrombophilia factors can increase this risk, particularly in individuals with severe symptoms and elevated CA125 levels.

Fluoxetine Successfully Treats Intracranial Enterovirus E18 Infection in a Patient with CD79a Deficiency Arising from Segmental Uniparental Disomy of Chromosome 19.

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.

Qualitative Immunoglobulin Deficiency Causes Bacterial Infections in Patients with STAT1 Gain-of-Function Mutations.

PURPOSES: STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy. METHODS: Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity. RESULTS: All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts. CONCLUSION: STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels.

Atypical familial hemophagocytic lymphohistiocytosis type 3 in children: A report of cases and literature review.

BACKGROUND: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is caused by UNC13D variants. The clinical manifestations of FHL3 are highly diverse and complex. Some patients exhibit atypical or incomplete phenotypes, making accurate diagnosis difficult. Our study aimed to broaden the understanding of the atypical FHL3 clinical spectrum. METHODS: In our study, we analyzed in detail the clinical features of four Chinese patients with UNC13D variants. Additionally, we conducted a comprehensive review of the existing literature on previously reported atypical manifestations and summarized the findings. RESULTS: Two of our patients presented with muscle involvement, while the other two had hematological involvement; none of them met the diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). However, protein expression and functional analysis ultimately confirmed diagnostic criteria for FHL3 in all patients. From the literature we reviewed, many atypical FHL3 patients had neurological involvement, especially isolated neurological manifestations. At the same time, arthritis and hypogammaglobulinemia were also prone to occur. CONCLUSION: Our study highlights that the expression of the Munc13-4 protein may not fully indicate the pathogenicity of UNC13D variants, whereas CD107a analysis could be more sensitive for disease diagnosis. These findings contribute to a broader understanding of the FHL3 clinical spectrum and may offer new insights into the underlying pathogenesis of UNC13D variants. It is crucial to prioritize the timely and accurate diagnosis of atypical patients, as they may often be overlooked among individuals with rheumatic or hematological diseases.

Case Report: Can preoperative implantation of veno-arterial extracorporeal membrane oxygenation lead to embolic events in infective endocarditis?

Early-stage infective endocarditis (IE) can lead to severe complications, including infarctions and metastatic infections caused by inflammatory embolus shedding. Common embolism sites include the brain, spleen, kidneys, lungs, and intestines. Additionally, acute heart failure (AHF) can occur in up to 40% of cases, and its presence can impact the clinical outcomes of patients with IE. Cardiogenic shock (CGS) is often more likely to occur after AHF has taken place. If bacteria invade the blood, infectious shock can occur. Patients with IE can experience simple CGS, septic shock, or a combination of the two. Extracorporeal membrane oxygenation (ECMO) typically serves as a Bridge for Heart failure and Cardiogenic shock. Previous research indicates that there are limited reports of ECMO support for patients with IE after CGS has occurred. Because CGS may occur at any time during IE treatment, it is important to understand the timing of ECMO auxiliary support and how to carry out comprehensive treatment after support. Timely treatment can help to reduce or avoid the occurrence of serious complications and improve the prognosis of patients with IE. Our work combines a case study to review the ECMO support of IE patients after CGS through a literature review. Overall, we suggest that when patients with IE have large bacterial thrombosis and a greater risk of shedding, it is recommended to carefully evaluate the indications and contraindications for ECMO after discussion by a multidisciplinary team (MDT). Still, active surgical treatment at an early stage is recommended.

Population-based BRCA germline mutation screening in the Han Chinese identifies individuals at risk of BRCA mutation-related cancer: experience from a clinical diagnostic center from greater Shanghai area.

BACKGROUND: Deleterious BRCA1/2 (BRCA) mutation raises the risk for BRCA mutation-related malignancies, including breast, ovarian, prostate, and pancreatic cancer. Germline variation of BRCA exhibits substantial ethnical diversity. However, there is limited research on the Chinese Han population, constraining the development of strategies for BRCA mutation screening in this large ethnic group. METHODS: We profile the BRCA mutational spectrum, including single nucleotide variation, insertion/deletion, and large genomic rearrangements in 2,080 apparently healthy Chinese Han individuals and 522 patients with BRCA mutation-related cancer, to determine the BRCA genetic background of the Chinese Han population, especially of the East Han. Incident cancer events were monitored in 1,005 participants from the healthy group, comprising 11 BRCA pathogenic/likely pathogenic (PLP) variant carriers and 994 PLP-free individuals, including 3 LGR carriers. RESULTS: Healthy Chinese Han individuals demonstrated a distinct BRCA mutational spectrum compared to cancer patients, with a 0.53% (1 in 189) prevalence of pathogenic/likely pathogenic (PLP) variant, alongside a 3 in 2,080 occurrence of LGR. BRCA1 c. 5470_5477del demonstrated high prevalence (0.44%) in the North Han Chinese and penetrance for breast cancer. None of the 3 LGR carriers developed cancer during the follow-up. We calculated a relative risk of 135.55 (95% CI 25.07 to 732.88) for the development of BRCA mutation-related cancers in the BRCA PLP variant carriers (mean age 42.91 years, median follow-up 10 months) compared to PLP-free individuals (mean age 48.47 years, median follow-up 16 months). CONCLUSION: The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

CXCL family-related classification predicts prognosis and response to immunotherapy in patients with head and neck squamous cell carcinoma based on TCGA and GEO databases.

Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignant cancer worldwide. The cysteine X cysteine (CXC) chemokine family contains 17 members, which are reportedly crucial for the growth, invasion, metastasis, and microenvironment of tumor cells. Although the precise functions of CXC ligands (CXCLs) in HNSCC are unclear, these proteins may play important roles in controlling tumor growth and forming the tumor immune environment. Methods: We downloaded the RNA sequencing and matched clinicopathological data of 379 patients with HNSCC as the training set from The Cancer Genome Atlas and two datasets from the Gene Expression Omnibus for use as validation sets. Results: Through consensus clustering, we identified two subtypes of HNSCC associated with the CXCL family, named cluster1 and cluster2. Patients with the cluster1 subtype showed favourable clinical outcomes, significant immune cell infiltration, and improved immune response signalling pathway modulation. We also developed a nomogram of CXCL family scores for therapeutic use and for predicting the overall survival (OS) of patients with HNSCC. Patients with lower scores showed longer OS and higher immune cell infiltration in their tissues. Conclusions: We developed a new classification method for HNSCC using the CXCL gene family, which can be used clinically to evaluate the prognosis and response to immunotherapy in patients with HNSCC.

Risk factors for hypoactive delirium in patients with nontraumatic ARDS: a prospective observational study.

To investigate the incidence, characteristics and risk factors for hypoactive delirium in patients with nontraumatic acute respiratory distress syndrome (ARDS) and to explore the independent risk factors associated with hypoactive delirium and provide new ideas for early prediction and treatment. Hypoactive delirium is a known serious complication in ARDS patients, and currently, there are no effective early detection models or clinical prediction tools, and there is a lack of clinical treatment. This study included nontraumatic ARDS patients who stayed in the intensive care unit (ICU) for more than 24 h and were older than 18 years. A total of 205 ARDS patients admitted to the ICU of Gansu Provincial People's Hospital between December 2021 and February 2023 were selected. Demographic data, clinical characteristics and laboratory test results were collected within 24 h after the patients entered the ICU. Multivariate logistic regression analysis was used to investigate risk factors, evaluate the clinical prediction effect of the model and construct a nomogram for visual display. The incidence of hypoactive delirium among the patients included in the study was 41%. Patients with hypoactive delirium had hypertension; diabetes mellitus; Acute Physiology and Chronic Health Evaluation II (APACHE II) scores ≥ 15; and increased procalcitonin, C-reactive protein (CRP), lactic dehydrogenase and interleukin-6 (IL-6) levels compared with those without hypoactive delirium. Logistic regression analysis revealed that diabetes mellitus (OR 3.305, 95% CI: 1.866-12.616; p = 0.047), CRP level (OR 1.002, 95% CI: 1.001-1.023; p = 0.044), and IL-6 level (OR 1.045, 95% CI: 1.017-1.063; p = 0.001) were independent risk factors for hypoactive delirium. After receiver operating characteristic (ROC) curve analysis, calibration plot and decision curve analysis (DCA) confirmed that the clinical prediction ability of this study model was satisfactory, and a nomogram was drawn for visual display. Hypoactive delirium is a common serious complication in nontraumatic ARDS patients. Our logistic regression model not only effectively predicts hypoactive delirium early but also reveals potential clinical therapeutic targets.

A Multienzyme Reaction-Mediated Electrochemical Biosensor for Sensitive Detection of Organophosphorus Pesticides.

Ethephon (ETH), a commonly employed growth regulator, poses potential health risks due to its residue in fruits and vegetables, leading to both acute and subchronic toxicity. However, the detection accuracy of ETH is compromised by the color effects of the samples during the detection process. In this work, a multienzyme reaction-mediated electrochemical biosensor (MRMEC) was developed for the sensitive, rapid, and color-interference-resistant determination of ETH. Nanozymes Fe3O4@Au-Pt and graphene nanocomplexes (GN-Au NPs) were prepared as catalysts and signal amplifiers for MRMEC. Acetylcholinesterase (AChE), acetylcholine (ACh), and choline oxidase (CHOx) form a cascade enzyme reaction to produce H2O2 in an electrolytic cell. Fe3O4@Au-Pt has excellent peroxidase-like activity and can catalyze the oxidation of 3,3',5,5'-tetramethvlbenzidine (TMB) in the presence of H2O2, resulting in a decrease in the characteristic peak current of TMB. Based on the inhibitory effect of ETH on AChE, the differential pulse voltammetry (DPV) current signal of TMB was used to detect ETH, offering the limit of detection (LOD) of 2.01 nmol L-1. The MRMEC method effectively analyzed ETH levels in mangoes, showing satisfactory precision (coefficient of variations, 2.88-15.97%) and recovery rate (92.18-110.72%). This biosensor holds promise for detecting various organophosphorus pesticides in food samples.