A Rapid Detection Method for H3 Avian Influenza Viruses Based on RT-RAA.

The continued evolution of H3 subtype avian influenza virus (AIV)-which crosses the interspecific barrier to infect humans-and the potential risk of genetic recombination with other subtypes pose serious threats to the poultry industry and human health. Therefore, rapid and accurate detection of H3 virus is highly important for preventing its spread. In this study, a method based on real-time reverse transcription recombinase-aided isothermal amplification (RT-RAA) was successfully developed for the rapid detection of H3 AIV. Specific primers and probes were designed to target the hemagglutinin (HA) gene of H3 AIV, ensuring highly specific detection of H3 AIV without cross-reactivity with other important avian respiratory viruses. The results showed that the detection limit of the RT-RAA fluorescence reading method was 224 copies/response within the 95% confidence interval, while the detection limit of the RT-RAA visualization method was 1527 copies/response within the same confidence interval. In addition, 68 clinical samples were examined and the results were compared with those of real-time quantitative PCR (RT-qPCR). The results showed that the real-time fluorescence RT-RAA and RT-qPCR results were completely consistent, and the kappa value reached 1, indicating excellent correlation. For visual detection, the sensitivity was 91.43%, the specificity was 100%, and the kappa value was 0.91, which also indicated good correlation. In addition, the amplified products of RT-RAA can be visualized with a portable blue light instrument, which enables rapid detection of H3 AIV even in resource-constrained environments. The H3 AIV RT-RAA rapid detection method established in this study can meet the requirements of basic laboratories and provide a valuable reference for the early diagnosis of H3 AIV.

The AP-2 Family of Transcription Factors-Still Undervalued Regulators in Gastroenterological Disorders.

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/ß/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2ß and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future.

Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies.

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.

A new perspective on the regulation of glucose and cholesterol transport by mitochondria-lysosome contact sites.

Mitochondria and lysosomes play a very important role in maintaining cellular homeostasis, and the dysfunction of these organelles is closely related to many diseases. Recent studies have revealed direct interactions between mitochondria and lysosomes, forming mitochondria-lysosome contact sites that regulate organelle network dynamics and mediate the transport of metabolites between them. Impaired function of these contact sites is not only linked to physiological processes such as glucose and cholesterol transport but also closely related to the pathological processes of metabolic diseases. Here, we highlight the recent progress in understanding the mitochondria-lysosome contact sites, elucidate their role in regulating metabolic homeostasis, and explore the potential implications of this pathway in metabolic disorders.

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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by symptoms such as abdominal pain, diarrhea, constipation, and indigestion. Given its unclear etiology and pathogenesis, and the absence of specific biomarkers, clinical diagnosis and treatment of IBS continue to pose significant challenges. In recent years, metabolomics technology, known for its non-invasive, high-throughput, high-precision, and highly reproducible features, has been widely applied in the diagnosis, treatment, and prognosis of various diseases. Therefore, metabolomics technology is expected to offer novel insights and methodologies for the biological mechanism research, diagnosis, and treatment of IBS. This article reviews recent advancements in the application of metabolomics to IBS, exploring its potential value in the clinical diagnosis and treatment of children with this condition.

Bundled care combined with animated educational videos can promote the recovery of severe pneumonia in children: A case-control study.

In this study, we analyzed the efficacy of animated educational videos and group nursing in the treatment of severe pneumonia in children. A total of 140 patients with severe pneumonia in our hospital from October 2022 to October 2023 were selected as the research subjects, and they were divided into a control group and an observation group. The control group received routine care, while the observation group received animated educational videos and cluster nursing interventions. The treatment effects of the 2 groups of patients were compared. Clinical indicators such as body temperature recovery time, blood oxygen saturation recovery time, heart rate recovery time, consciousness recovery time, and respiratory rate recovery time were compared between the 2 groups of patients. The results showed that the temperature recovery time, oxygen saturation recovery time, heart rate recovery time and respiratory rate recovery time in observation group were significantly different from those in control group (P < .05). Univariate analysis showed that families with or without anxiety disorder had statistically significant differences in economic conditions, extrapulmonary complications, nursing methods and other aspects. Logistic multivariate regression analysis showed that nursing methods, extrapulmonary complications, and poor economic conditions (income < 5000) were risk factors for anxiety among family members of severe pneumonia patients, while good economic conditions (income > 5000) were protective factors. So, animated educational videos and bundled care can effectively improve the nursing effectiveness of children with severe pneumonia and promote their recovery.

Simultaneous determination of sixteen phthalic acid esters (PAEs) in soil and evaluation of matrix effect using a QuEChERS/GC/MS-internal standard method.

Phthalic acid esters (PAEs) are emerging pollutants that need to be analyzed precisely. Chromatography-based determination of PAE content in soils are frequently affected by matrix effect, which may limit the quantification of different kinds of PAEs from different types of soil. Here we optimized a QuEChERS protocol combined with gas chromatography-mass spectrometry (GC-MS) for simultaneous determination of 16 PAEs in different soils. PAEs in different type of soils (fluvo-aquic soil, red soil, and black soil) were extracted with acetonitrile followed by GC-MS detection based on quantitative ion internal standard method. All 16 PAEs showed excellent linear relationships with mass peak areas (R2 > 0.99). The limits of detection (LOD) and limits of quantitation (LOQ) of all the samples were in the range of 0.91-66.97 µg/kg and 2.7-200.9 µg/kg, respectively. The accurate test at 0.5, 0.1, and 1.0 mg/kg spiking level recorded recovery rate between 80.11% and 100.99% with relative standard deviations (RSDs) ranging from 0.37 to 8.50% in tested matrices. No significant matrix effect was observed for most tested PAEs. This is a simple method with high sensitivity and strong stability, which is suitable and reproducible for quantifying large number of PAEs in different types of soil.

Dynamic-to-static switch of hydrogen bonds induces a metal-insulator transition in an organic-inorganic superlattice.

Hydrogen bonds profoundly influence the fundamental chemical, physical and biological properties of molecules and materials. Owing to their relatively weaker interactions compared to other chemical bonds, hydrogen bonds alone are generally insufficient to induce substantial changes in electrical properties, thus imposing severe constraints on their applications in related devices. Here we report a metal-insulator transition controlled by hydrogen bonds for an organic-inorganic (1,3-diaminopropane)0.5SnSe2 superlattice that exhibits a colossal on-off ratio of 107 in electrical resistivity. The key to inducing the transition is a change in the amino group's hydrogen-bonding structure from dynamic to static. In the dynamic state, thermally activated free rotation continuously breaks and forms transient hydrogen bonds with adjacent Se anions. In the static state, the amino group forms three fixed-angle positions, each separated by 120°. Our findings contribute to the understanding of electrical phenomena in organic-inorganic hybrid materials and may be used for the design of future molecule-based electronic materials.

Quantum-Confined Tunable Ferromagnetism on the Surface of a Van der Waals Antiferromagnet NaCrTe2.

The surface of three-dimensional materials provides an ideal and versatile platform to explore quantum-confined physics. Here, we systematically investigate the electronic structure of Na-intercalated CrTe2, a van der Waals antiferromagnet, using angle-resolved photoemission spectroscopy and ab initio calculations. The measured band structure deviates from the calculation of bulk NaCrTe2 but agrees with that of ferromagnetic monolayer CrTe2. Consistently, we observe unexpected exchange splitting of the band dispersions, persisting well above the Néel temperature of bulk NaCrTe2. We argue that NaCrTe2 features a quantum-confined 2D ferromagnetic state in the topmost surface layer due to strong ferromagnetic correlation in the CrTe2 layer. Moreover, the exchange splitting and the critical temperature can be controlled by surface doping of alkali-metal atoms, suggesting the feasibility of tuning the surface ferromagnetism. Our work not only presents a simple platform for exploring tunable 2D ferromagnetism but also provides important insights into the quantum-confined low-dimensional magnetic states.

The uncertainties and certainties of gene transcription in a human tumor cell.

Previously we have identified that the expression number and levels of oncogenes and antioncogenes are highly positively or negatively associated with major cellular progress in a cancer cell. However, we have not defined any cellular potentials of a human tumor cell at the level of the overall gene expression. Here, we counted the overall number of expression genes and overall counts of mRNA in depth and revealed that the expression levels of mRNA were directly associated with the expression number of genes in a human tumor cell. Gene expression networks revealed steady states of tricarboxylic acid (TCA) cycle and ATP production, differentiation potentials that might be disturbed and blocked by uncertain gene expressing networks, and potential capabilities to undergo epithelial-mesenchymal transition (EMT), neurogenesis, angiogenesis, inflammatory response, immune evasion, and metastasis in a human tumor cell. Our analysis identifies unpredictable gene expression characteristics in human tumor cells. The results might profoundly influence mechanisms how a human tumor cell generates and undergoes its progresses.

Jin-Gu-Lian Capsule Did Not Significantly Improve Clinical Value in Rheumatoid Arthritis Therapy: A Real-World Study.

Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.

Design and test of controlling frequency circulating fan system in bulk curing barn.

Objective: Scientific control of wind speed between tobacco leaves can improve quality of tobacco after cured in bulk curing barn. Method: Regarding the light orange color after cured tobacco and high power consumption caused by inaccurate control of the current circulating fan, and different requirements for wind speed during the tobacco curing, this paper designed a variable frequency drive system (VDS) to control the rotation speed of the circulating fan. With the design of anti-interference components, the VDS is integrated with the curing controller. Results: The curing adoption of anti-interference for the VDS device will not affect the normal operation of the tobacco curing controller during tobacco curing. Compared with the traditional circulating fan with high speed and low speed options, the VDS device can accurately control the air speed during the tobacco curing process, and improve the economic characters and internal quality of cured tobacco. This paper is also to provide an alternative method in terms of ventilation and humidity removal for industrial and agricultural production.

Application of protein engineering to ene-reductase for the synthesis of chiral compounds through asymmetric reaction.

Ene-reductase (ER) has been widely applied for asymmetrical synthesis of chiral intermediates due to its substrate promiscuity, photoexcited reactivity, and excellent property with producing two chiral centers at a time. Natural ERs often exhibit the same stereoselectivity, and they need to be engineered for opposite configuration of chiral compounds. The hydrogenation process toward activated alkenes by ERs is composed of reductive half reaction and oxidative half reaction, which are dependent upon two cofactors NAD(P)H and flavin mononucleotide. The catalytic activity of ERs will be affected by the size of the substrate, the activating strength of the electron-withdrawing groups, redox potential of cofactors, and the loop flexibility around catalytic cavity. Currently, protein engineering to ERs has been successfully employed to enhance various catalytic properties, including photoexcited asymmetric synthesis. This review summarizes the approaches to reverse the stereoselectivity and enhance catalytic activity of ERs and new applications of the engineered ERs in photobiocatalytic asymmetric synthesis, besides the discussion with the existing molecular mechanisms of mutants regarding the improved catalytic performance.

DOSage of Exercise for chronic low back pain disorders (DOSE): protocol for a systematic review with dose-response network meta-analysis.

Chronic low back disorders are the leading cause of direct and indirect healthcare burden globally. Exercise training improves pain intensity, mental health and physical function. However, the optimal prescription variables are unknown. We aim to compare the efficacy of various exercise dosages for chronic low back disorders to identify the optimal prescription variables. Six databases (Medline, SPORTDiscus, CINAHL, PsycINFO, EMBASE and CENTRAL), trial registries (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) and reference lists of prior systematic reviews will be searched, and we will conduct forward and backward citation tracking. We will include peer-reviewed randomised controlled trials (individual, cluster or cross-over trials) published in English or German language comparing exercise training to other exercise training or non-exercise training interventions (conservative, non-surgical, non-pharmacological, non-invasive treatments, placebo, sham, usual/standard care, no-treatment control, waitlist control) in adults with chronic low back disorders. Outcomes will include pain intensity, disability, mental health, adverse events, adherence rate, dropout rate and work capacity. Version 2 of the Cochrane risk-of-bias tool will be employed. The dose will be categorised as cumulative dose (total and weekly minutes of exercise training) and individual dose prescription variables (intervention duration, session duration, frequency and intensity). Dose-response model-based network meta-analysis will be used to assess the comparative efficacy of different exercise doses to determine a dose-response relationship. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation. Information about optimal exercise training dosage will help in enhancing treatment outcomes.

Pushing Pressure Detection Sensitivity to New Limits by Modulus-Tunable Mechanism.

Only microstructures are used to improve the sensitivity of iontronic pressure sensors. By modulating the compressive modulus, a breakthrough in the sensitivity of the iontronic pressure sensor is achieved. Furthermore, it allows for programmatic tailoring of sensor performance according to the requirements of different applications. Such a new strategy pushes the sensitivity up to a record-high of 25 548.24 kPa-1 and expands the linear pressure range from 15 to 127 kPa. Additionally, the sensor demonstrates excellent mechanical stability over 10 000 compression-release cycles. Based on this, a well-controlled robotic hand that precisely tracks the pressure behavior inside a balloon to autonomously regulate the gripping angle is developed. This paves the way for the application of iontronic pressure sensors in precise sensing scenarios.

Superconductivity in pressurized trilayer La4Ni3O10-δ single crystals.

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.

Inflammatory factors and the risk of urolithiasis: a bidirectional Mendelian randomization study.

Background: Urolithiasis is a prevalent condition encountered in urology. Over the past decade, its global incidence has been on an upward trajectory; paired with a high recurrence rate, this presents considerable health and economic burdens. Although inflammatory factors are pivotal in the onset and progression of urolithiasis, their causal linkages remain elusive. Method: Mendelian randomization (MR) is predicated upon genome-wide association studies (GWASs). It integrates bioinformatics analyses to reveal causal relationships between exposures and outcomes, rendering it an effective method with minimized bias. Drawing from a publicly accessible GWAS meta-analysis comprising 8,293 samples, we identified 41 genetic variations associated with inflammatory cytokines as instrumental variables. Outcome data on upper urinary tract stones, which included renal and ureteral stones (9,713 cases and 366,693 controls), and lower urinary tract stones, including bladder and urethral stones (1,398 cases and 366,693 controls), were derived from the FinnGen Consortium R9 dataset. By leveraging the bidirectional MR methodology, we aimed to decipher the causal interplay between inflammatory markers and urolithiasis. Results: Our study comprehensively elucidated the association between genetic inflammatory markers and urolithiasis via bidirectional Mendelian randomization. Post-MR analysis of the 41 genetic inflammation markers revealed that elevated levels of circulating interleukin-2 (IL-2) (OR = 0.921, 95% CI = 0.848-0.999) suggest a reduced risk for renal stone disease, while heightened stem cell growth factor beta (SCGF-ß) (OR = 1.150, 95% CI = 1.009-1.310) and diminished macrophage inflammatory protein 1 beta (MIP-1ß) (OR = 0.863, 95% CI = 0.779-0.956) levels suggest an augmented risk for lower urinary tract stones. Furthermore, renal stone disease appeared to elevate IL-2 (ß = 0.145, 95% CI = 0.013-0.276) and cutaneous T cell-attracting chemokine (CTACK) (ß = 0.145, 95% CI = 0.013-0.276) levels in the bloodstream, whereas lower urinary tract stones were linked to a surge in interleukin-5 (IL-5) (ß = 0.142, 95% CI = 0.057-0.226), interleukin-7 (IL-7) (ß = 0.108, 95% CI = 0.024-0.192), interleukin-8 (IL-8) (ß = 0.127, 95% CI = 0.044-0.210), growth regulated oncogene alpha (GRO-α) (ß = 0.086, 95% CI = 0.004-0.169), monokine induced by interferon-gamma (MIG) (ß = 0.099, 95% CI = 0.008-0.191) and macrophage inflammatory protein 1 alpha (MIP-1α) (ß = 0.126, 95% CI = 0.044-0.208) levels. Conclusion: These discoveries intimate the instrumental role of IL-2 in the onset and progression of upper urinary tract stones. SCGF-ß and MIP-1ß influence the development of lower urinary tract stones. Urolithiasis also impacts the expression of cytokines such as IL-2, CTACK, IL-5, IL-7, IL-8, GRO-α, MIG, and MIP-1α. There is a pressing need for further investigation to ascertain whether these biomarkers can be harnessed to prevent or treat urolithiasis.

Sources and control of impurity during one-pot enzymatic production of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis. This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes. KEY POINTS: • A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD • Both SwiKR and GDH are identified with ketosteroid isomerase activity. • Development of catalytic strategy to control by-product and achieve highly selective DHEA production.