Mechanisms underlying delirium in patients with critical illness.

Delirium is an acute, global cognitive disorder syndrome, also known as acute brain syndrome, characterized by disturbance of attention and awareness and fluctuation of symptoms. Its incidence is high among critically ill patients. Once patients develop delirium, it increases the risk of unplanned extubation, prolongs hospital stay, increases the risk of nosocomial infection, post-intensive care syndrome-cognitive impairment, and even death. Therefore, it is of great importance to understand how delirium occurs and to reduce the incidence of delirium in critically ill patients. This paper reviews the potential pathophysiological mechanisms of delirium in critically ill patients, with the aim of better understanding its pathophysiological processes, guiding the formulation of effective prevention and treatment strategies, providing a basis for clinical medication.

Construction and evaluation of a liver cancer risk prediction model based on machine learning.

BACKGROUND: Liver cancer is one of the most prevalent malignant tumors worldwide, and its early detection and treatment are crucial for enhancing patient survival rates and quality of life. However, the early symptoms of liver cancer are often not obvious, resulting in a late-stage diagnosis in many patients, which significantly reduces the effectiveness of treatment. Developing a highly targeted, widely applicable, and practical risk prediction model for liver cancer is crucial for enhancing the early diagnosis and long-term survival rates among affected individuals. AIM: To develop a liver cancer risk prediction model by employing machine learning techniques, and subsequently assess its performance. METHODS: In this study, a total of 550 patients were enrolled, with 190 hepatocellular carcinoma (HCC) and 195 cirrhosis patients serving as the training cohort, and 83 HCC and 82 cirrhosis patients forming the validation cohort. Logistic regression (LR), support vector machine (SVM), random forest (RF), and least absolute shrinkage and selection operator (LASSO) regression models were developed in the training cohort. Model performance was assessed in the validation cohort. Additionally, this study conducted a comparative evaluation of the diagnostic efficacy between the ASAP model and the model developed in this study using receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA) to determine the optimal predictive model for assessing liver cancer risk. RESULTS: Six variables including age, white blood cell, red blood cell, platelet counts, alpha-fetoprotein and protein induced by vitamin K absence or antagonist II levels were used to develop LR, SVM, RF, and LASSO regression models. The RF model exhibited superior discrimination, and the area under curve of the training and validation sets was 0.969 and 0.858, respectively. These values significantly surpassed those of the LR (0.850 and 0.827), SVM (0.860 and 0.803), LASSO regression (0.845 and 0.831), and ASAP (0.866 and 0.813) models. Furthermore, calibration and DCA indicated that the RF model exhibited robust calibration and clinical validity. CONCLUSION: The RF model demonstrated excellent prediction capabilities for HCC and can facilitate early diagnosis of HCC in clinical practice.

Palladium-Catalyzed Cyclization and Direct Arylation of 1-[2-(2,2-Dibromoethenyl)phenyl]-1H-pyrrole with Allenes.

A novel and efficient palladium-catalyzed highly regioselective reaction of 1-[2-(2,2-dibromoethenyl)phenyl]-1H-pyrrole with allenes was realized to synthesize pyrrolo[1,2-a]quinolones. The tandem process involves intermolecular cyclization and intramolecular direct arylation, leading to the formation three new C-C bonds and two new rings. Notably, this transformation exhibits broad substrate scope and high functional group tolerance.

Mental Health Literacy Among Urban and Rural Residents of Guangdong Province, China.

Purpose: The study aims to understanding the mental health literacy level of urban and rural residents in Guangdong Province, the first major province in China, and its influencing factors is crucial. Methods: A multi-stage stratified equal-volume random sampling method was adopted in October-December 2022 to select permanent residents aged 18 years and above in Guangdong Province for the questionnaire survey, which consisted of a general demographic information questionnaire and a national mental health literacy questionnaire. Rao-Scott χ²-test with correction based on sampling design, independent samples t-test and binary multivariate logistic regression analysis were performed. Results: A total of 51744 individuals completed the questionnaire, including 31822 urban residents and 19200 rural residents. The rate of achievement of mental health literacy was 13.6% among urban residents, which was significantly higher compared to the rate of 8.6% among rural residents. Logistic regression analysis showed that female, higher education, being mental worker, being a retiree, having a higher monthly household income, maintaining a regular diet, and using electronic products for 2-6 hours per day were protective factors for mental health literacy attainment in urban residents, while having chronic diseases, being a smoker and having a history of drinking were identified as risk factors in urban residents. Among in rural residents, married, younger, higher education, being mental worker and using electronic products for 2-6 hours per day, maintaining a regular diet, and engaging in regular exercise were protective factors for achieving mental health literacy, while previous smoking was a risk factor. Conclusion: The study revealed a low level of mental health literacy among urban and rural residents of Guangdong Province, with a significant disparity between the two areas. These findings highlight the need for continuing efforts to increase the dissemination of mental health knowledge in rural communities and improve levels of mental health literacy.

Synthesis of ß-ionone from xylose and lignocellulosic hydrolysate in genetically engineered oleaginous yeast Yarrowia lipolytica.

ß-ionone, an apocarotenoid derived from a C40 terpenoid has an intense, woody smell and a low odor threshold that has been widely used in as an ingredient in food and cosmetics. Yarrowia lipolytica is a promising host for ß-ionone production because of its oleaginous nature, its ability to produce high levels of acetyl-CoA (an important precursor for terpenoids), and the availability of synthetic biology tools to engineer the organism. In this study, ß-carotene-producing Y. lipolytica strain XK17 was employed for ß-ionone biosynthesis. First, we explored the effect of different sources of carotenoid cleavage dioxygenase (CCD) genes on ß-ionone production. A high-yielding strain rUinO-D14 with 122 mg/L of ß-ionone was obtained by screening promoters combined with rDNA mediated multi-round iterative transformations to optimize the expression of the CCD gene of Osmanthus fragrans. Second, to further develop a high-level production strain for ß-ionone, we optimized key genes in the mevalonate pathway by multi-round iterative transformations mediated by non-homologous end joining, combined with a protein tagging strategy. Finally, the introduction of a heterologous oxidoreductase pathway enabled the engineered Y. lipolytica strain to use xylose as a sole carbon source and produce ß-ionone. In addition, the potential for use of lignocellulosic hydrolysate as the carbon source for ß-ionone production showed that the NHA-A31 strain had a high ß-ionone productivity level. This study demonstrates that engineered Y. lipolytica can be used for the efficient, green and sustainable production of ß-ionone.

Association of hemoglobin glycation index with clinical outcomes in patients with coronary artery disease: a prospective cohort study.

BACKGROUND: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD). METHODS: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups. CONCLUSION: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD.

Associations between peripheral whole blood cell counts derived indexes and cancer prognosis: An umbrella review of meta-analyses of cohort studies.

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.

2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore.

Introduction: Psoriasis is a multisystem, chronic, inflammatory dermatological disease. In routine clinical practice, the management of psoriasis varies significantly. The current study aimed to develop a set of practice guidelines relevant to dermatology practice in Singapore. Method: The Psoriasis Therapeutic Guidelines Workgroup, comprising members of the Dermato-logical Society of Singapore with a subspecialisation in psoriasis, was convened to develop the guidelines. Clinical questions on selected topics were generated and refined by the workgroup. A literature search using PubMed was performed on their assigned topics from June 2013 to December 2023. The articles were included and graded based on the level of evidence. Results: The guidelines address topics ranging from clinical assessment to practical considerations in the management of mild, moderate and severe psoriasis, including delivery of care, referrals to specialists and adherence to treatment. The recommended therapies include phototherapy, methotrexate, acitretin, cyclosporine; apremilast; topical corticoste-roids, calcipotriol, topical calcineurin inhibitors; and biologics (i.e. adalimumab, infliximab, secukinumab, ixekizumab, ustekinumab, etanercept) either in combina-tion or as monotherapy. Common therapeutic concerns relating to biologic use were addressed. Recommendations on generalised pustular psoriasis, palmoplantar pustular psoriasis and psoriatic arthritis were also made. Patients on systemic therapy would receive appropriate vaccine counselling. Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. Conclusion: These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.

Molecular characterization of common zoonotic protozoan parasites and bacteria causing diarrhea in dairy calves in Ningxia Hui Autonomous Region, China.

Diarrhea caused by zoonotic pathogens is one of the most common diseases in dairy calves, threatening the health of young animals. Humans are also at risk, in particular children. To explore the pathogens causing diarrhea in dairy calves, the present study applied PCR-based sequencing tools to investigate the occurrence and molecular characteristics of three parasites (Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi) and three bacterial pathogens (Escherichia coli, Clostridium perfringens, and Salmonella spp.) in 343 fecal samples of diarrheic dairy calves from five farms in Lingwu County, Ningxia Hui Autonomous Region, China. The total positive rate of these pathogens in diarrheic dairy calves was 91.0% (312/343; 95% CI, 87.9-94.0), with C. perfringens (61.5%, 211/343; 95% CI, 56.3-66.7) being the dominant one. Co-infection with two to five pathogens was found in 67.3% (231/343; 95% CI, 62.4-72.3) of investigated samples. There were significant differences (p < 0.05) in the positive rates of Cryptosporidium spp. and diarrheagenic E. coli among farms, age groups, and seasons. Two Cryptosporidium species (C. parvum and C. bovis) and five gp60 subtypes of C. parvum (IIdA15G1, IIdA20G1, IIdA19G1, IIdA14G1, and a novel IIdA13G1) were identified. Two assemblages (assemblage E and zoonotic assemblage A) of G. duodenalis and six ITS genotypes of E. bieneusi (J, Henan-IV, EbpC, I, EbpA, and ESH-01) were observed. Four virulence genes (eaeA, stx1, stx2, and st) of diarrheagenic E. coli and one toxin type (type A) of C. perfringens were detected. Our study enriches our knowledge on the characteristics and zoonotic potential of diarrhea-related pathogens in dairy calves.

Title: Caractérisation moléculaire des protozoaires parasites zoonotiques courants et des bactéries responsables de diarrhée chez les veaux laitiers dans la région autonome Hui du Ningxia, en Chine. Abstract: La diarrhée causée par des agents pathogènes zoonotiques est l'une des maladies les plus courantes chez les veaux laitiers, menaçant la santé des jeunes animaux. Ceci est également un risque pour la santé humaine, en particulier les enfants. Pour explorer les agents pathogènes responsables de la diarrhée chez les veaux laitiers, cette étude a utilisé des outils de séquençage basés sur la PCR pour étudier l'occurrence et les caractères moléculaires de trois parasites (Cryptosporidium spp., Giardia duodenalis et Enterocytozoon bieneusi) et de trois agents pathogènes bactériens (Escherichia coli, Clostridium perfringens et Salmonella spp.) dans 343 échantillons fécaux de veaux laitiers diarrhéiques provenant de cinq fermes du comté de Lingwu, région autonome Hui du Ningxia, en Chine. Le taux total positif de ces pathogènes chez les veaux laitiers diarrhéiques était de 91,0 % (312/343; IC à 95 %, 87,9­94,0), et C. perfringens (61,5 %, 211/343; IC à 95 %, 56,3­66,7) était le plus répandu. Une co-infection avec deux à cinq pathogènes a été trouvée dans 67,3 % (231/343; IC à 95 %, 62,4­72,3) des échantillons étudiés. Il y avait des différences significatives (p < 0,05) dans les taux positifs de Cryptosporidium spp. et d'E. coli diarrhéogènes entre les fermes, les groupes d'âge et les saisons. Deux espèces de Cryptosporidium (C. parvum et C. bovis) et cinq sous-types de gp60 de C. parvum (IIdA15G1, IIdA20G1, IIdA19G1, IIdA14G1 et un nouveau, IIdA13G1) ont été identifiés. Deux assemblages (assemblage E et assemblage zoonotique A) de G. duodenalis et six génotypes ITS d'E. bieneusi (J, Henan-IV, EbpC, I, EbpA et ESH-01) ont été observés. Quatre gènes de virulence (eaeA, stx1, stx2 et st) d'E. coli diarrhéogènes et un type de toxine (type A) de C. perfringens ont été détectés. Notre étude enrichit les connaissances sur les caractères et le potentiel zoonotique des agents pathogènes liés à la diarrhée chez les veaux laitiers.

Metal-organic frameworks with two different-sized aromatic ring-confined nanotraps for benchmark natural gas upgrade.

Recovery of light alkanes from natural gas is of great significance in petrochemical production. Herein, a promising strategy utilizing two types of size-complementary aromatic ring-confined nanotraps (called bi-nanotraps here) is proposed to efficiently trap ethane (C2H6) and propane (C3H8) selectively at their respective sites. Two isostructural metal-organic frameworks (MOFs, SNNU-185/186), each containing bi-nanotraps decorated with six aromatic rings, are selected to demonstrate the feasibility of this method. The smaller nanotrap acts as adsorption sites tailored for C2H6 while the larger one is optimized in size for C3H8. The separation is further facilitated by the large channels, which serve as mass transfer pathways. These advanced features give rise to multiple C-H⋯π interactions and size/shape-selective interaction sites, enabling SNNU-185/186 to achieve high C2H6 adsorption enthalpy (43.5/48.8 kJ mol-1) and a very large thermodynamic interaction difference between C2H6 and CH4. Benefiting from the bi-nanotrap effect, SNNU-185/186 exhibits benchmark experimental natural gas upgrade performance with top-level CH4 productivity (6.85/6.10 mmol g-1), ultra-high purity and first-class capture capacity for C2H6 (1.23/0.90 mmol g-1) and C3H8 (2.33/2.15 mmol g-1).

The influence of COVID-19 on short-term mortality in acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the differences in short-term mortality risk between acute ischemic stroke (AIS) patients with and without SARS-CoV-2 infection. METHODS: PubMed, EMBASE, Scopus, and Cochrane Databases were systematically searched from December 1, 2019 to May 20, 2022 using the keywords coronavirus disease 2019 (COVID-19), COVID-19, SARS-CoV-2, and ischemic stroke. A random-effects model was estimated, and subgroup analysis and meta-regressions were performed. The quality of eligible studies was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 26 eligible studies with 307,800 patients were included in this meta-analysis. The overall results show that in-hospital and 90-day mortality was 3.31-fold higher in AIS with SARS-CoV-2 patients compared with those without SARS-CoV-2. When matched for age and National Institutes of Health Stroke Scale score at admission, the risk ratio of in-hospital mortality from AIS among patients with SARS-CoV-2 versus without decreased to 2.83. Reperfusion therapy and endovascular thrombectomy may further reduce the risk of death in patients to some extent but do not increase the incidence of symptomatic intracerebral hemorrhage. Meta-regression showed that in-hospital mortality decreased with increasing National Institutes of Health Stroke Scale score in AIS with SARS-CoV-2 compared to those without SARS-CoV-2 and that the difference in mortality risk between the 2 was independent of age and sex. CONCLUSIONS: The results of this study suggest that AIS patients with SARS-CoV-2 have higher short-term mortality compared to AIS patients without SARS-CoV-2, and reperfusion and endovascular thrombectomy therapy may reduce the risk of short-term mortality to some extent. The differences in in-hospital mortality risk were similar across ages and sexes. Focused attention is therefore needed on AIS patients with SARS-CoV-2 to control mortality.

Customizing Ionic Liquids Functionalized MOFs Composites with Hydrophobic Interface for Electrochemical CO2 Reduction.

The electrochemical carbon dioxide reduction reaction (CO2RR) to generate feedstocks for chemical products (e.g., carbon monoxide, CO) offers a highly attractive method for achieving the closure of the carbon cycle. Ionic liquids (ILs)-functionalized Cu-based catalyst Cu2O-HKUST-1/IL1/PTFE was developed, configuring metal-organic frameworks(MOFs) based materials with high adsorption and multiple active sites. The modified electrocatalysts exhibited high specific surface area, strong CO2 adsorption capacity, abundant active sites, and fast charge transfer rate. The nucleophilic active site of deprotonation at the C2 site in imidazole ILs further improved the selectivity of proton migration and CO product generation, which was verified through DFT calculations for the low Gibbs free energy of the generated intermediate interactions. In addition, the hydrophobic interface constructed by PTFE facilitated the inhibition of the hydrogen evolution reaction (HER) and significantly improved the efficiency of CO2 electroreduction. The Cu2O-HKUST-1/IL1/PTFE catalyst manifested a high C1 Faraday efficiency (FE) up to 96.5% and in particular 92.7% for FECO at -1.7 V vs RHE. The present work provides an efficient strategy for configuring ILs-functionalized MOFs-based materials with good hydrophobic interfaces to enhance the efficiency of CO2 electroreduction to C1 products.

Acupuncture Provides Short-Term Functional Improvements and Pain Relief for Patients After Knee Replacement Surgery: A Systematic Review and Meta-analysis.

The impact of acupuncture on knee function and pain intensity following knee replacement remains controversial. Therefore, we categorized the postsurgery recovery period into 3 phases: short-term (≤2 weeks), intermediate-term (2 weeks-3 months), and long-term (>3 months), and then assessed the effectiveness of acupuncture in improving function and alleviating pain at different stages following knee replacement. This meta-analysis included randomized controlled trials that compared acupuncture intervention with either no treatment or a sham group after knee replacement. Six databases were searched from inception to December 31, 2023, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and 2 Chinese databases (Chinese National Knowledge Infrastructure and WanFang Data). A total of 23 studies comprising 1,464 participants were included. Significant improvement of active range of motion was observed on day 7 and week 2 after operation. Lower pain intensity at rest was noted in patients receiving acupuncture in short-term periods after operation (12 hours, day 1, day 2, day 5, and week 2). A reduction in pain intensity during movement with acupuncture was observed on postoperative day 1 and day 7. Auricular acupuncture did not show not significant effectiveness in improving range of motion and pain intensity. For conventional acupuncture, the combination of distal and local point selection was found to be the most effective. Early application of acupuncture, in conjunction with physical therapy, starting before postoperative day 1 or day 2, was recommended. Further high-quality researches are warranted to validate the findings in this meta-analysis. PERSPECTIVE: This article demonstrates that acupuncture has short-term effects (≤2 weeks) on improving active range of motion and reducing pain during rest and during movement following knee replacement surgery. The findings support the early application of acupuncture in hospital settings after knee replacement. REGISTRATION ID: The study was registered on PROSPERO (CRD42024503479).

Enhancement of Synergistic Photocatalytic Performance by Anchoring Cadmium Sulfide on Nanosphere Structured Coordination Polymers.

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

Distinct clinical characteristics and prognosis of pediatric-onset growth hormone-secreting pituitary adenoma (GHPA) patients compared to adult-onset patients.

PURPOSE: To explore the clinical characteristics, treatment, and prognosis of growth hormone-secreting pituitary adenoma (GHPA) patients with pediatric-onset, so as to facilitate clinical management. METHODS: A retrospective cohort study was carried out between 102 pediatric-onset GHPA patients admitted to our hospital from January 2013 to June 2022 and 204 adult-onset GHPA patients who were randomly matched. RESULTS: GHPA with pediatric-onset was predominantly male, associated with higher proportion of genetic syndromes, longer course, and delayed diagnosis. Clinical symptoms of visual field defects and menstrual abnormality were more common. The pediatric-onset group exhibited higher growth hormone (GH) nadir during oral glucose tolerance test (OGTT), higher rates of hyperprolactinemia, larger maximum diameter of adenoma, and higher rates of optic chiasm compression, suprasellar invasion, and pituitary apoplexy. Hypertension, diabetes, and obstructive sleep apnea-hypopnea syndrome (OSAHS) were more common in the adult-onset group. Echocardiography results were similar between the two groups. The pediatric-onset group owned significantly higher treatment scores and proportions of multimodal therapy modality, more surgical complications, and a higher proportion of ki67 ≥ 3%. There was no significant difference in the final cure rate, but male patients with adult-onset had a worse prognosis. The recurrence rate was also similar between two groups. Hypopituitarism was more prevalent in the pediatric-onset group, while the adult-onset group had a higher incidence of other tumors. CONCLUSION: Pediatric-onset GHPA patients exhibit distinct clinical characteristics compared to adult-onset patients. Multimodal therapy modalities could help to achieve a cure rate comparable to that of adult-onset patients.

TRPC3/6 Channels Mediate Mechanical Pain Hypersensitivity via Enhancement of Nociceptor Excitability and of Spinal Synaptic Transmission.

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

Abnormal T Cells Function Associated With Intraspinal Cold Abscess Caused by Macrolide-resistant Mycoplasma pneumoniae in a Patient With X-linked Agammaglobulinemia.

Intraspinal cold abscesses caused by macrolide-resistant Mycoplasma pneumoniae in patients with X-linked agammaglobulinemia have not yet been described to our knowledge. Here we describe a patient with X-linked agammaglobulinemia who developed an intraspinal cold abscess caused by macrolide-resistant M. pneumoniae . Genetic analysis revealed a hemizygous c.1566 + 1G > C (IVS15 + 1G > C) mutation in BTK gene. The patient showed relatively naive T cells and a significant proliferative defect.

When anaphylactic shock meets epinephrine and blood lactate increases: A case report.

RATIONALE: Anaphylactic shock, a severe and rapid systemic allergic reaction, poses significant treatment challenges. Epinephrine, the first-line treatment, effectively reverses symptoms but can complicate the clinical picture by elevating lactate levels, blurring the distinction between shock-induced hypoperfusion and drug-induced metabolic effects. PATIENT CONCERNS: A 26-year-old female presented with anaphylactic shock following an antibiotic infusion, experiencing chest tightness, hypotension, and pulmonary edema, without significant past medical history apart from a noted allergy to fish and shrimp. DIAGNOSES: Anaphylaxis was diagnosed based on clinical presentation and supported by imaging that revealed pulmonary edema, despite normal troponin levels and electrocardiogram. INTERVENTIONS: Treatment included 0.5 mg of intramuscular epinephrine and 5 mg of intravenous dexamethasone, with subsequent intubation and mechanical ventilation in the intensive care unit. An intravenous epinephrine infusion was also administered for hemodynamic support. OUTCOMES: While epinephrine resolved the pulmonary edema and stabilized circulation, it led to a significant, albeit transient, increase in lactate levels, which normalized following discontinuation of epinephrine, indicating the metabolic effect of the drug rather than ongoing tissue hypoperfusion. LESSONS: This case illustrates the importance of recognizing epinephrine-induced lactate elevation in anaphylactic shock, necessitating a nuanced interpretation of lactate dynamics. Clinicians must differentiate between lactate elevations due to tissue hypoperfusion and those arising from epinephrine's pharmacologic effects to optimize patient care.

An integrative framework reveals widespread gene flow during the early radiation of oaks and relatives in Quercoideae (Fagaceae).

Although the frequency of ancient hybridization across the Tree of Life is greater than previously thought, little work has been devoted to uncovering the extent, timeline, and geographic and ecological context of ancient hybridization. Using an expansive new dataset of nuclear and chloroplast DNA sequences, we conducted a multifaceted phylogenomic investigation to identify ancient reticulation in the early evolution of oaks (Quercus). We document extensive nuclear gene tree and cytonuclear discordance among major lineages of Quercus and relatives in Quercoideae. Our analyses recovered clear signatures of gene flow against a backdrop of rampant incomplete lineage sorting, with gene flow most prevalent among major lineages of Quercus and relatives in Quercoideae during their initial radiation, dated to the Early-Middle Eocene. Ancestral reconstructions including fossils suggest ancestors of Castanea + Castanopsis, Lithocarpus, and the Old World oak clade probably co-occurred in North America and Eurasia, while the ancestors of Chrysolepis, Notholithocarpus, and the New World oak clade co-occurred in North America, offering ample opportunity for hybridization in each region. Our study shows that hybridization-perhaps in the form of ancient syngameons like those seen today-has been a common and important process throughout the evolutionary history of oaks and their relatives. Concomitantly, this study provides a methodological framework for detecting ancient hybridization in other groups.