A narrow-bandgap RuI3 nanoplatform to synergize radiotherapy, photothermal therapy, and thermoelectric dynamic therapy for tumor eradication.

Therapeutic resistance is an essential challenge for nanotherapeutics. Herein, a narrow bandgap RuI3 nanoplatform has been constructed firstly to synergize radiotherapy (RT), photothermal therapy (PTT), and thermoelectric dynamic therapy (TEDT) for tumor eradication. Specifically, the photothermal performance of RuI3 can ablate tumor cells while inducing TEDT. Noteworthy, the thermoelectric effect is found firstly in RuI3, which can spontaneously generate an electric field under the temperature gradient, prompting carrier separation and triggering massive ROS generation, thus aggravating oxidative stress level and effectively inhibiting HSP-90 expression. Moreover, RuI3 greatly enhances X-ray deposition owing to its high X-ray attenuation capacity, resulting in a pronounced computed tomography imaging contrast and DNA damage. In addition, RuI3 possesses both catalase-like and glutathione peroxidase-like properties, which alleviate tumor hypoxia and reduce antioxidant resistance, further exacerbating 1O2 production during RT and TEDT. This integrated therapy platform combining PTT, TEDT, and RT significantly inhibits tumor growth. STATEMENT OF SIGNIFICANCE: RuI3 nanoparticles were synthesized for the first time. RuI3 exhibited the highest photothermal properties among iodides, and the photothermal conversion efficiency was 53.38 %. RuI3 was found to have a thermoelectric effect, and the power factor could be comparable to that of most conventional thermoelectric materials. RuI3 possessed both catalase-like and glutathione peroxidase-like properties, which contributed to enhancing the effect of radiotherapy.

Research on multilateral collaboration strategies in agricultural seed quality assurance.

Seeds, as the initial products in agricultural systems, play a pivotal role in ensuring quality, fundamental to national food security and sustainable agricultural development. This study introduces a concept integrating public governance and evolutionary game theory to construct a quadripartite evolutionary game model involving seed companies, certification agencies, farmers, and governmental departments. It considers the strategic choices of these stakeholders under varying economic motivations and market mechanisms, as well as the influence of external regulation and incentives on game strategies. The existence conditions for evolutionarily stable strategy combinations are determined using the Lyapunov first method, and MATLAB is employed for numerical simulation analysis to validate the game analysis under initial conditions. The simulation results reveal two potential equilibrium points corresponding to different strategic choices among stakeholders. The study finds that producing high-quality seeds and the refusal of certification agencies to engage in rent-seeking are crucial for ensuring seed quality. Additionally, the cost-benefit ratio of seed companies, the speculative cost of certification agencies, and the rights-protection cost of farmers are key determinants in the evolution of seed quality assurance strategies. This research also holds practical significance in enhancing seed quality assurance mechanisms and fostering sustainable development in agriculture.

Do Weather Conditions Still Have an Impact on the COVID-19 Pandemic? An Observation of the Mid-2022 COVID-19 Peak in Taiwan.

Since the onset of the COVID-19 pandemic in 2019, the role of weather conditions in influencing transmission has been unclear, with results varying across different studies. Given the changes in border policies and the higher vaccination rates compared to earlier conditions, this study aimed to reassess the impact of weather on COVID-19, focusing on local climate effects. We analyzed daily COVID-19 case data and weather factors such as temperature, humidity, wind speed, and a diurnal temperature range from 1 March to 15 August 2022 across six regions in Taiwan. This study found a positive correlation between maximum daily temperature and relative humidity with new COVID-19 cases, whereas wind speed and diurnal temperature range were negatively correlated. Additionally, a significant positive correlation was identified between the unease environmental condition factor (UECF, calculated as RH*Tmax/WS), the kind of Climate Factor Complex (CFC), and confirmed cases. The findings highlight the influence of local weather conditions on COVID-19 transmission, suggesting that such factors can alter environmental comfort and human behavior, thereby affecting disease spread. We also introduced the Fire-Qi Period concept to explain the cyclic climatic variations influencing infectious disease outbreaks globally. This study emphasizes the necessity of considering both local and global climatic effects on infectious diseases.

Clinical application value of metagenome next-generation sequencing in pulmonary diffuse exudative lesions: a retrospective study.

Objective: This study aims to investigate the clinical application value of Metagenome Next-Generation Sequencing (mNGS) for pulmonary diffuse exudative lesions. Methods: From January 1, 2014, to November 31, 2021, 136 cases with chest radiologic presentations of pulmonary diffuse exudative lesions admitted to Fujian Provincial Hospital were included in the study; of those, 77 patients underwent mNGS pathogen detection. Based on the pathogen detection outcomes and clinical diagnoses, patients were categorized into an infection group (IG) and a non-infection group (NIG). A comparison was made between the diagnostic efficacy of the mNGS technique and traditional culture methods. Meanwhile, 59 patients clinically identified as having infectious pulmonary diffuse exudative lesions but who did not receive mNGS testing were designated as the non-NGS infection group (non-IG). A retrospective cohort study was conducted on patients in both the IG and non-IG, with a 30-day all-cause mortality endpoint used for follow-up. Outcomes: When compared to conventional culture methods, mNGS demonstrated an approximate 35% increase in sensitivity (80.0% vs 45.5%, P<0.001), without significant disparity in specificity (77.3% vs 95.5%, P=0.185). Under antibiotic exposure, the positivity rate detected by mNGS was notably higher than that by traditional culture methods, indicating that mNGS is less affected by exposure to antibiotics (P<0.05). Within 30 days, the all-cause mortality rate for patients in the IG versus the non-IG was 14.55% and 37.29%, respectively (P<0.05). Following a COX regression analysis to adjust for confounding factors, the analysis revealed that a CURB-65 score ≥3 points (HR=3.348, P=0.001) and existing cardiovascular disease (HR=2.473, P=0.026) were independent risk factors for these patients. Conversely, mNGS testing (HR=0.368, P=0.017) proved to be an independent protective factor. Conclusion: mNGS technology makes it easier to pinpoint the cause of pulmonary diffuse infectious exudative lesions without much interference from antibiotics, helping doctors spot and diagnose these issues early on, thereby playing a key role in helping them decide the best treatment approach for patients. Such conclusions may have a bias, as the performance of traditional methods might be underestimated due to the absence of complete results from other conventional diagnostic techniques like serological testing and PCR.

Exotic Magnetism in Perovskite KOsO_{3}.

A new perovskite KOsO_{3} has been stabilized under high-pressure and high-temperature conditions. It is cubic at 500 K (Pm-3m) and undergoes subsequent phase transitions to tetragonal at 320 K (P4/mmm) and rhombohedral (R-3m) at 230 K as shown from refining synchrotron x-ray powder diffraction (SXRD) data. The larger orbital overlap integral and the extended wave function of 5d electrons in the perovskite KOsO_{3} allow to explore physics from the regime where Mott and Hund's rule couplings dominate to the state where the multiple interactions are on equal footing. We demonstrate an exotic magnetic ordering phase found by neutron powder diffraction along with physical properties via a suite of measurements including magnetic and transport properties, differential scanning calorimetry, and specific heat, which provide comprehensive information for a system at the crossover from localized to itinerant electronic behavior.

Bifunctional Metal-Organic Nanoballs Featuring Lewis Acidic and Basic Sites as a New Platform for One-Pot Tandem Catalysis.

The design and synthesis of polyhedra using coordination-driven self-assembly has been an intriguing research area for synthetic chemists. Metal-organic polyhedra are a class of intricate molecular architectures that have garnered significant attention in the literature due to their diverse structures and potential applications. Hereby, we report Cu-MOP, a bifunctional metal-organic cuboctahedra built using 2,6-dimethylpyridine-3,5-dicarboxylic acid and copper acetate at room temperature. The presence of both Lewis basic pyridine groups and Lewis acidic copper sites imparts catalytic activity to Cu-MOP for the tandem one-pot deacetalization-Knoevenagel/Henry reactions. The effect of solvent system and time duration on the yields of the reactions was studied, and the results illustrate the promising potential of these metal-organic cuboctahedra, also known as nanoballs for applications in catalysis.

DDX21 mediates co-transcriptional RNA m6A modification to promote transcription termination and genome stability.

N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.

Design and simulation of light field patterns for angular color variation reduction in micro-LED and mini-LED RGB arrays.

We propose a methodology to mitigate angular color variation in full-color micron-scale LED arrays. By simulating light field distribution for red (AlGaAs) and green/blue (GaN) light across various RGB micro-LED sizes, we can select matching light field patterns for RGB chips, reducing angular color variation from 0.0201 to 0.0030. Applying this method to full-color mini-LED assemblies achieves a reduction from 0.0128 to 0.0032 by matching light field patterns with varying substrate thicknesses. This straightforward approach aligns with current mass transfer processes, offering practical implementation.

Li Promoting Long Afterglow Organic Light-Emitting Transistor for Memory Optocoupler Module.

The artificial brain is conceived as advanced intelligence technology, capable to emulate in-memory processes occurring in the human brain by integrating synaptic devices. Within this context, improving the functionality of synaptic transistors to increase information processing density in neuromorphic chips is a major challenge in this field. In this article, Li-ion migration promoting long afterglow organic light-emitting transistors, which display exceptional postsynaptic brightness of 7000 cd m-2 under low operational voltages of 10 V is presented. The postsynaptic current of 0.1 mA operating as a built-in threshold switch is implemented as a firing point in these devices. The setting-condition-triggered long afterglow is employed to drive the photoisomerization process of photochromic molecules that mimic neurotransmitter transfer in the human brain for realizing a key memory rule, that is, the transition from long-term memory to permanent memory. The combination of setting-condition-triggered long afterglow with photodiode amplifiers is also processed to emulate the human responding action after the setting-training process. Overall, the successful integration in neuromorphic computing comprising stimulus judgment, photon emission, transition, and encoding,  to emulate the complicated decision tree of the human brain is demonstrated.

Long-term outcomes of intestinal penetrating Crohn's disease following successful nonoperative management.

There is a paucity of data on the surgical or medical treatment for abscess/fistula complicating Crohn's disease after successful nonsurgical management. We conducted a cohort study to investigate the long-term outcomes and the risk factors for the requirement of subsequent surgical intervention in Crohn's disease patients with complicating fistulas/abscess following successful nonsurgical management. Data were collected on penetrating Crohn's disease experiencing successful nonsurgical treatment between December 2012 and December 2021. Long-term outcomes and risk factors of surgery were assessed by univariate and multivariate analysis, and subgroup analysis was performed based on penetrating phenotype including abscess, fistula, and phlegmon. A total of 523 penetrating Crohn's disease patients; there were 390, 125, and 60 patients complicated with fistulas, abscess, and phlegmon, respectively. Long-term outcomes showed that BMI < 18.5 (kg/m2), the recurrent abscess, and stricture were independent risk factors of surgery. Biologics and resolution of abscess were independent protective factors of surgery. Furthermore, in 399 patients undergoing early surgery, stricture and BMI < 18.5 (kg/m2) were independent risk factors, and biologics and abscess resolution were protective of the early surgery. Subgroup analysis based on fistula, abscess, and phlegmon phenotype also demonstrated that concomitant stricture was an independent risk factor and the use of biologics was protective of surgical resection. Our data indicate that biologics can delay the requirement of surgery and may be given to patients with penetrating complicating Crohn's disease who have been successfully treated nonoperatively, but surgical resection should be considered in the setting of malnutrition and stenosis formation.

A neural m6A pathway regulates behavioral aggregation in migratory locusts.

RNA N6-methyladenosine (m6A), as the most abundant modification of messenger RNA, can modulate insect behaviors, but its specific roles in aggregation behaviors remain unexplored. Here, we conducted a comprehensive molecular and physiological characterization of the individual components of the methyltransferase and demethylase in the migratory locust Locusta migratoria. Our results demonstrated that METTL3, METTL14 and ALKBH5 were dominantly expressed in the brain and exhibited remarkable responses to crowding or isolation. The individual knockdown of methyltransferases (i.e., METTL3 and METTL14) promoted locust movement and conspecific attraction, whereas ALKBH5 knockdown induced a behavioral shift toward the solitary phase. Furthermore, global transcriptome profiles revealed that m6A modification could regulate the orchestration of gene expression to fine tune the behavioral aggregation of locusts. In summary, our in vivo characterization of the m6A functions in migratory locusts clearly demonstrated the crucial roles of the m6A pathway in effectively modulating aggregation behaviors.

Investigation of the Correlation between Enterovirus Infection and the Climate Factor Complex Including the Ping-Year Factor and El Niño-Southern Oscillation in Taiwan.

Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model.

Three-dimensional ultrafast charge-density-wave dynamics in CuTe.

Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.

Ectopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma.

BACKGROUND: Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. METHODS: We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. RESULTS: The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. CONCLUSION: Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment.

Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function.

Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.

Antigen/HLA-agnostic strategies for Characterizing Tumor-responsive T cell receptors in PDAC patients via single-cell sequencing and autologous organoid application.

Characterization of tumor-responsive T cell receptors (TCRs) is a critical step in personalized TCR-T cell therapy, and remains challenging for pancreatic ductal adenocarcinoma (PDAC). Here we report a proof-of-concept study to identify and validate antitumor TCRs in two representative PDAC patients using ultradeep single-cell TCR/RNA sequencing and autologous organoids, and reveal the phenotypic dynamics of TCR repertoire in different T cell expansions from the same patient. We first performed comparative sequencing on freshly harvested peripheral blood mononuclear cells (PBMCs) and uncultured tumor infiltrating lymphocytes (TILs), followed by reactivity tests of TIL-enriched TCRs with autologous organoids, in which two tumor-responsive TCRs were successfully characterized and the corresponding TILs were mostly tissue-resident memory-like T cells, and partially expressed both naïve and exhausted T cell markers. For the PDAC patient without high-quality TILs, PBMCs were cultured with neoantigen peptide (KRASG12D), organoids, or anti-CD3 antibody in presence, and experienced extensive clonal expansions within ten days. All derived PBMCs were sequenced in parallel (>82,000 cells), and TCRs enriched in both peptide- and organoid-experienced, but not anti-CD3-treated CD8 T cells, were assessed for their reactivity to antigen-presenting cells (APCs) and organoids, in which three neoantigen-reactive TCRs were identified as tumor-responsive, and the corresponding T cells were characterized by mixed transcriptional signatures including but not limited to typical exhausted T cell markers. Together, our study revealed that the combination of ultradeep single-cell sequencing and organoid techniques enabled rapid characterization of tumor-responsive TCRs for developing practical personalized TCR-T therapy in an antigen/human leukocyte antigen (HLA)-agnostic manner.

OXCT1 regulates hippocampal neurogenesis and alleviates cognitive impairment via the Akt/GSK-3ß/ß-catenin pathway after subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease that usually has a poor prognosis. Neurogenesis is a potential therapeutic target for brain injury. Ketone metabolism also plays neuroprotective roles in many neurological disorders. OXCT1 (3-Oxoacid CoA-Transferase 1) is the rate-limiting enzyme of ketone body oxidation. In this study, we explored whether increasing ketone oxidation by upregulating OXCT1 in neurons could promote neurogenesis after SAH, and evaluated the potential mechanism involved in this process. METHODS: The ß-hydroxybutyrate content was measured using an enzymatic colorimetric assay. Adeno-associated virus targeting neurons was injected to overexpress OXCT1, and the expression and localization of proteins were evaluated by western blotting and immunofluorescence staining. Adult hippocampal neurogenesis was evaluated by dual staining with doublecortin and 5-Ethynyl-2'-Deoxyuridine. LY294002 was intracerebroventricularly administered to inhibit Akt activity. The Morris water maze and Y-maze tests were employed to assess cognitive function after SAH. RESULTS: The results showed that OXCT1 expression and hippocampal neurogenesis significantly decreased in the early stage of SAH. Overexpression of OXCT1 successfully increased hippocampal neurogenesis via activation of Akt/GSK-3ß/ß-catenin signaling and improved cognitive function, both of which were reversed by administration of LY294002. CONCLUSIONS: OXCT1 regulated hippocampal ketone body metabolism and increased neurogenesis through mechanisms mediated by the Akt/GSK-3ß/ß-catenin pathway, improving cognitive impairment after SAH.

The impact of delayed closure of ileostomy on postoperative complications in patients with Crohn's disease: a case-matched study.

Ileostomy creation is a common procedure to mitigate postoperative complications in Crohn's disease (CD) patients. However, the optimal timing for ileostomy closure remains controversial. This study aims to investigate whether delayed ileostomy closure (> 6 months post formation) affects postoperative complications compared to early closure (≤ 6 months post formation). Consecutive CD patients who underwent ileostomy reversal at a tertiary care center between January 1, 2013, and December 1, 2021, were included. The study compared patients who underwent early ileostomy closure to matched patients undergoing delayed ileostomy closure. The 90-day postoperative complications were compared between the two groups. The study included 352 eligible patients for ileostomy reversion. Our data showed that patients undergoing delayed ileostomy closure had higher incidence of ileostomy-related infectious complications (12% vs. 4%, p = 0.008), a longer postoperative hospital stay (10 days with an IQR of 7-12 days versus 8 days with an IQR of 7-11 days, p = 0.024), and increased rate of ileus (28% versus 15%, p = 0.003). There were 256 patients included after 1:1 propensity score matching. The results revealed no significant differences in postoperative hospital stay, infectious or non-infectious complications except for a statistically significant increase in the incidence of ileus in the delayed closure group (p = 0.01). Patients undergoing delayed ileostomy closure has similar outcomes to early closure in terms of postoperative complications, except for a higher incidence of ileus.

RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.

BACKGROUND: Ceramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM. METHODS: RNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood-brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein-protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results. RESULTS: RNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway. CONCLUSION: RPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.