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Local oral microbiota are closely related to the tumorigenesis and therapeutic response of oral cancer. In this study, we have validated that oral commensal Porphyromonas gingivalis ( P. gingivalis ) is highly responsible for chemoresistance and contributes to the poor therapeutic outcome of traditional chemotherapy. Accordingly, the biologically derived nanovesicles from ginger (GDNVs) with excellent P. gingivalis elimination ability are explored to transport the clinically used drug paclitaxel (PTX) for potentiating the therapeutic efficiency. Taking advantage of active targeting and inhibition abilities of GDNVs against P. gingivalis , the PTX-loaded GDNVs nanosystem (P-GDNVs) can enrich in the P. gingivalis -colonized tumor tissues and effectively inhibit the growth of P. gingivalis for downregulating the IL-6/pSTAT3/P-gp pathway, thereby reducing the efflux of intracellular drugs to overcome chemoresistance. By evaluating both P. gingivalis -infected tumor cells and P. gingivalis -infiltrated tumor-bearing mice, P-GDNVs show a much enhanced tumor cell killing effect, as compared with free PTX. This naturally occurring nanotherapeutic system represents an effective bioactive material for targeted elimination of host microbiota to boost therapeutic response, showing great promise to combat commensal microbiota-rich tumors.

Peroxynitrite (ONOO - ), as an important reactive nitrogen species, plays a pivotal role in the regulation of intracellular redox homeostasis, signal transduction, cell growth and metabolism, and other physiological processes. Organelles are important for regulating ONOO - , and the dysregulation of ONOO - in organelles is closely related to various diseases. Therefore, it is essential to monitor ONOO - in cellular organelles, including mitochondria, lysosome, endoplasmic reticulum (ER), Golgi apparatus, and lipid droplets. However, the latest advances in organelle-targeting ONOO - fluorescent probes have not been reviewed systematically. In this review, we focus on the design, sensing mechanism, and organelle-targeting imaging applications of ONOO - fluorescent probes that were reported since 2018. This review will help to facilitate the comprehension of organelle-targeting fluorescent probes for the detection of ONOO - .

In our report, we present the case of a 60-year-old adult with symptomatic indirect carotid-cavernous fistulas (CCFs). All venous outflow routes from the cavernous sinus were absent except for an engorged left superficial middle cerebral vein, which extended through the left vein of Labbé to the left transverse sinus and then to right transverse-sigmoid sinus. We approached the diseased cavernous sinus retrogradely, starting from the right femoral vein and passing through the right transverse-sigmoid sinus, left transverse sinus, and left vein of Labbé, ultimately reaching the left CCFs. Embolization was performed using coils, successfully obliterating the fistulas without complications. This case represents the second reported approach through the vein of Labbé for CCFs and the first using a trans-Labbé vein from a contralateral approach (video 1), proving advantageous by avoiding an acute angle between the vein of Labbé and the ipsilateral sigmoid sinus.1-6neurintsurg;jnis-2024-022311v1/V1F1V1Video 1Embolization of CCF using a Trans-Labbé vein from a contralateral approach.‍., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The fall armyworm (FAW), Spodoptera frugiperda , is a major polyphagous pest that mainly feeds on maize and other cash crops. Understanding S. frugiperda 's behavior on different host plants facilitates the development of effective integrated pest management (IPM) plans. Therefore, this study investigated the oviposition preferences of S. frugiperda females among different host plants using no-choice, two-choice, and multiple-choice bioassays. In no-choice bioassays, para grass, Urochloa mutica (Forssk.) (Poales: Poaceae); maize, Zea mays (L.) (Poales: Poaceae); and napier grass, Pennisetum purpureum (Schumach) (Poales: Poaceae) were identified as highly attractive, while sweet sorghum, Sorghum dochna (Forssk.) (Poales: Poaceae); sunhemp, Crotalaria juncea (L.) (Fabales:Fabacea); Egyptian clover, Trifolium alexandrinum (L.) (Fabales:Fabacea); desmodium, Desmodium uncinatum (Jacq.) (Fabales:Fabacea); natal grass, melinis repens (Zizka) (Poales: Poaceae); molasses grass, Melinis minutiflora (P.Beauv.) (Poales: Poaceae); and mung bean, Vigna radiata (R. wilczek) (Fabales: Fabaceae) exhibited reduced oviposition effects. Two-choice bioassays revealed different levels of attractiveness and repellency among different plant combinations. In multiple-choice bioassays, mimicking an intercropping scenario, differences in the number of eggs and egg mass were observed for M:S:D:W (maize, sunhemp, desmodium, and cage wall), S:D:M:W (sunhemp, desmodium, maize, and cage wall), and D:M:S:W (desmodium, maize, sunhemp, and cage wall). This study provides insights into the egg-laying preferences of S. frugiperda females among different host plants, valuable for the management of S. frugiperda . This encourages further research and further identification of novel repellent and attractant host plants, which will ultimately contribute to the development of sustainable and environmentally friendly crop production practices and techniques.

Objective: To compare the diagnostic rate and safety of postoperative complications between transbronchial cryobiopsy (TBCB) and transbronchial lung biopsy (TBLB) in patients with lung transplantation. Methods: A retrospective analysis of patients who underwent TBCB or TBLB in the Department of Lung Transplantation in China-Japan Friendship Hospital from June 2017 to June 2024 was conducted to determine the postoperative complications and analyze clinical characteristics, procedures, diagnostic rates and safety. Results: Thirty-five and 153 patients with lung transplantation received TBCB and TBLB, respectively. Patients who received TBCB had lower preoperative oxygenation index ( t' =2.4, P <0.01). Meanwhile, the pathological diagnosis rate (85.7% vs. 45.7%, χ ²=18.27, P <0.01) and clinical diagnosis rate (94.2% vs. 69.9%, χ ²=8.80, P <0.01) of patients who received TBCB were significantly higher than those who received TBLB. There was no significant difference in the incidence of severe bleeding (2.9% vs. 0.7%, χ ²=1.3, P =0.86) and pneumothorax (0 vs. 3.9%, χ ²=0.43, P =0.24) between patients receiving TBCB and TBLB. The most common complications after lung transplantation in the group of TBCB were chronic lung allograft dysfunction (45.4%, 15/33), antibody mediated rejection (18.2%, 6/33) and organizing pneumonia (12.2%, 4/33). While antibody mediated rejection (29.9%, 32/107), chronic lung allograft dysfunction (16.8%, 18/107), and pneumonia (16.8%, 18/107) were more frequent in the patients who received TBLB. Conclusions: TBCB has a high diagnostic value for postoperative complications after lung transplantation, with an acceptable complication rate of bleeding and pneumothorax.

Objective: Carpal tunnel syndrome (CTS) is a common neuromuscular disorder with an incidence rate of 4.9%. Research on the impact of Kinesio taping (KT) on electroneurography in individuals with CTS is limited, highlighting a significant gap in the literature. This study aimed to evaluate the effects of KT on palm numbness, pain intensity, hand grip strength, and median nerve electroneuromyography in individuals with mild to moderate CTS., Method: This was a randomized, controlled, parallel design study. Twenty-seven participants diagnosed with CTS through hospital outpatient clinics were randomly assigned to either the control or KT group. The outcome measurements included hand grip strength, the Boston Carpal Tunnel Questionnaire (BCTQ), and electroneurography, assessed at baseline and after 6 weeks of intervention. The statistical method used was non-parametric analysis, comparing differences with the median and interquartile range (IQR)., Results: Both the KT and control groups significantly improved the numbness grades, hand grip strength, and the BCTQ. The kinesio-taping group demonstrated an improvement in grip strength with a median increase of 2.21 kg (IQR: 0.65-3.79 kg), compared to the control group, which showed a median increase of only 0.70 kg (IQR: 0.22-1.45 kg). Statistical analysis revealed a significant difference between the two groups ( p  = 0.039), with an effect size of r  = 0.33., Conclusion: This study suggested that KT can be a supplementary treatment to relieve pain intensity, enhance hand grip strength, and improve sensory conduction velocity, motor latency, and motor amplitude., Clinical Trial Registration: https://doi.org/10.1186/ISRCTN82192319, ISRCTNregistry (No. ISRCTN82192319)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chen, Chou, Hsu, You, Wang, Cheng, Lui, Liu and Guo.)

Two new Cordyceps -like species, Perennicordycepszongqii and Purpureocilliumzongqii , isolated from a larva and soil, are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS, LSU, RPB2 and TEF ) support the establishment of the new species. Moreover, new species in the families Polycephalomycetaceae and Ophiocordycipitaceae were introduced into Tiankeng and the valley for the first time. Further attention needs to be paid to the diversity of other Cordyceps -like fungi in the special eco-environment of the karst region., Competing Interests: The authors have declared that no competing interests exist., (Wan-Hao Chen, Dan Li, Jian-Dong Liang, Xiu-Xiu Ren, Jie-Hong Zhao, Yan-Feng Han.)

Radiotherapy combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only a few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. Oral squamous cell carcinoma is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of Croton tonkinensis and Curcuma longa on cell viability in OSCC cells. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used. The anticancer effect and the mechanism of action of Croton tonkinensis and Curcuma longa in OSCC cells were analyzed by using cell viability assays, Western blot analysis, and Tranwell migration assays. The results showed that Croton tonkinensis concentration-dependently reduced the viability of OML1 and OML1-R (radioresistant) cells by downregulating the levels of AKT/mTOR mediators, such as p110α, p85, pAKT (ser473), p-mTOR (ser2448), and p-S6 Ribosomal (ser235/236). We found that cotreatment of OML1 and OML1R cells with either zVAD-FMK (apoptosis inhibitor), Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), or chloroquine (CQ, an autophagy inhibitor) markedly reduced cell death. These results demonstrate that Croton tonkinensis exhibits anti-proliferation activity and highlight the therapeutic potential of small-molecule inhibitors against PI3K/mTOR signaling for radiosensitization in HNC treatment.

Background: Two classes of newer glucose-lowering drugs (GLDs), sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, improve cardiovascular and renal outcomes among patients with type 2 diabetes (T2D). However, racial and ethnic minority groups carry higher cardiovascular risks but have lower access to newer GLDs. Contextual-level social determinants of health (SDOH) may be the underlying factor associated with newer GLD adoption., Objective: To identify the association between contextual-level SDOH and real-world adoption of newer GLDs among Medicare beneficiaries and to examine the nonstationarity in the associations., Methods: Data were from 15% random samples of January 2017 to December 2018 nationwide Medicare beneficiaries. We identified patients with T2D who did not use newer GLDs in the year before the index date-January 1, 2018-and followed the cohort for 1 year to record their status of initiating a newer GLD. We used a geographically weighted multivariable Poisson regression model to determine to what extent the SDOH-newer GLD initiation association (β coefficient) varied geographically., Results: We identified 795,469 eligible Medicare beneficiaries with T2D during the study period from our dataset. Of the study cohort, mean age was 73.1 (SD = 10.5) years, 424,312 (53.3%) were female, 562,994 (70.8%) were non-Hispanic White, 96,891 (12.2%) were non-Hispanic Black, 84,744 (10.6%) were Hispanic, and 29,645 (3.7%) were Asian/Pacific Islander. Newer GLD initiation was negatively associated with the percentage of the population reporting non-Hispanic Black race, Hispanic ethnicity, and unemployment, as revealed by nonspatial regression analyses. The county-level median household income was also associated with higher newer GLD initiation. The spatial analysis presented distinct distributions of local parameter estimates for each contextual-level SDOH., Conclusions: We identified key contextual-level SDOH associated with real-world adoption of newer GLDs and explored their geographic variation through spatially explicit, data-driven analytical approaches. Identifying areas of strong association between SDOH and newer GLD initiation is crucial for policymakers to allocate resources and develop interventions that address structural inequities.

The pervasive issue of microplastics in aquatic environments presents a formidable challenge to traditional water treatment methodologies, including those utilizing KMnO 4 . This study pioneers advanced oxidation processes (AOPs) method aimed at improving the degradation of PE microplastics by employing a dual treatment strategy that combines KMnO 4 oxidation with UV irradiation. Detailed analysis of the surface modifications and chemical functional groups of the treated PE microplastics revealed the establishment of Mn-O-Mn linkages on their surfaces. Weight reductions of 3.9%, 4.9%, and 7.5% were observed for the KMnO 4 /UVA, KMnO 4 /UVB, and KMnO 4 /UVC treatments over seven days, respectively. The emergence of carboxyl and hydroxyl groups played a crucial role in accelerating the degradation process. Notably, the combined application of UVC rays and KMnO 4 resulted in the most effective degradation of PE microplastics observed in our study. The process significantly enhanced the formation of MnO 2 particles from KMnO 4 oxidation, with concentrations ranging from 0.036 to 0.070 mM for KMnO 4 /UVA, 0.066-0.097 mM for KMnO 4 /UVB, and 0.086-0.180 mM for KMnO 4 /UVC. Furthermore, the influence of varying pH levels, KMnO 4 concentrations, and different water sources on the degradation efficacy was investigated. The pivotal role of free radicals and reactive manganese species in promoting the degradation of PE microplastics was identified. A comparative evaluation with treatments solely utilizing KMnO 4 or UV light highlighted the enhanced effectiveness of the combined approach, demonstrating its potential as an efficient solution for reducing microplastic contamination in aquatic systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To investigate the associations between time interval from myomectomy to pregnancy (TIMP) and subsequent pregnancy and obstetric complications, and to explore whether these associations vary according to maternal age at birth., Methods: A retrospective population-based cohort study was conducted from 2008 to 2017. Data were extracted from the National Health Insurance Research Database and the Taiwan Maternal and Child Health Database, comprising 2024 379 births from 1 391 856 pregnancies. Eligible cases were identified using diagnostic and procedure codes; 4006 first singleton births in 4006 women after their first laparotomic myomectomy were identified. We estimated the risks of pregnancy and obstetric outcomes according to TIMP (<6, 6-11, and ≥12 months). Subgroup analysis was performed by further dividing according to maternal age at birth (18-34 vs ≥35 years old)., Results: We observed higher risks of gestational hypertensive disorders (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.22-3.18, P = 0.005) and neonatal death (aOR 4.59, 95% CI 1.49-14.18, P = 0.008) for TIMP of <6 months versus TIMP of 6-11 months. Likewise, a TIMP ≥12 months was associated with increased risks of gestational hypertensive disorders (aOR 1.72, 95% CI 1.14-2.58, P = 0.010), and neonatal death (aOR 3.27, 95% CI 1.16-9.24, P = 0.025) versus a TIMP of 6-11 months. In subgroup analysis, women over 35 years old still had higher risks of gestational hypertensive disorders when TIMP was <6 months (aOR 2.26, 95% CI 1.17-4.37, P = 0.015) or ≥12 months (aOR 2.04, 95% CI 1.17-3.54, P = 0.012), and a higher risk of neonatal death when TIMP was <6 months (aOR 4.05, 95% CI 1.06-15.53, P = 0.041); whereas women aged 18-34 years old did not., Conclusions: This study suggests that a TIMP between 6 and 11 months is associated with lower risks of gestational hypertensive disorders and neonatal death compared with a TIMP <6 months or ≥12 months, especially for women over 35 years old., (© 2024 International Federation of Gynecology and Obstetrics.)

The quality of protective immunity plays a critical role in modulating vaccine efficacy, with native antigens often not able to trigger sufficiently strong immune responses for pathogen killing. This warrants creation of structure-based vaccine design, leveraging high-resolution antigen structures for mutagenesis to improve protein stability and efficient immunization strategies. Here, we investigated the mechanisms underlying structure-based vaccine design using CspZ-YA, a vaccine antigen from Borrelia burgdorferi , the bacteria causing Lyme disease (LD), the most common vector-borne disease in the Northern Hemisphere. Compared to wild-type CspZ-YA, we found CspZ-YA I183Y and CspZ-YA C187S required lower immunization frequency to protect mice from LD-associated manifestations and bacterial colonization. We observed indistinguishable human and mouse antigenicity between wild-type and mutant CspZ-YA proteins after native infection or active immunization. This supports our newly generated, high-resolution structures of CspZ-YA I183Y and CspZ-YA C187S , showing no altered surface epitopes after mutagenesis. However, CspZ-YA I183Y and CspZ-YA C187S favored the interactions between helices H and I, consistent with their elevated thermostability. Such findings are further strengthened by increasing ability of protective CspZ-YA monoclonal antibodies in binding to CspZ-YA at a physiological temperature (37°C). Overall, this study demonstrated enhanced intramolecular interactions improved long-term stability of antigens while maintaining protective epitopes, providing a mechanism for structure-based vaccine design. These findings can ultimately be extended to other vaccine antigens against newly emerging pathogens for the improvement of protective immunity.

This article studies the leader-following consensus problem for a class of linear multiagent systems over a directed graph with aperiodically sampled outputs. First, a novel distributed impulsive-observer-based consensus protocol is designed. This protocol requires only the output measurements at sporadic time instants for the observer and control gain design. Second, by using time-varying Lyapunov function techniques, sufficient conditions for exponential stability of a class of linear impulsive systems are established; subsequently, these stability results are applied for the distributed impulsive observer design. Different from the existing related works, the impulsive observer gain designed in this work is decoupled from the graph properties. As a result, once the impulsive observer gain is designed for one network topology, it can be directly used for other network topologies, as long as the graph properties and the dynamics of local agents satisfy certain conditions. Furthermore, the resilience of the designed protocol is tested under denial of service (DoS) attacks. It is shown that the protocol is robust with respect to low-frequency DoS attacks occurring in the observer communication network. Finally, two examples illustrating the validity and effectiveness of the proposed protocol are included.

Objective: To analyze the clinical characteristics of patients with pulmonary mucormycosis treated with and without surgery. Methods: This was a single-center, retrospective study. We retrieved "pulmonary mucormycosis" from the electronic medical records of China-Japan Friendship Hospital between 2016 and 2022. A total of 29 patients with pulmonary mucormycosis were collected. There were 19 males and 10 females with a median age of 49 (47, 67) years. Mann-Whitney U test, χ² test, Kaplan-Meier curve and log-rank test were used to compare the differences between groups. Results: The most common underlying disease was diabetes (19, 65.5%). The most frequent imaging findings were consolidation (25, 86.2%) and nodule or mass (21, 72.4%). Bronchial stenosis (16, 55.2%), obstruction by fungal plugs (18, 62.1%), pseudomembranous necrotizing bronchitis (19, 65.5%) were common. Treatment strategies were developed by the multi-disciplinary team (MDT). Among 16 patients who did not undergo surgery, 10 had bilateral multifocal lesions and 6 had unifocal lesions. All patients received antifungal therapies, and surgeries were performed in 13 (44.8%) patients. Patients who underwent surgery had numerically lower in-hospital mortality (15.4% vs. 31.3%, P =0.410). Involvement of unilateral multiple lesions was more common in patients who underwent surgeries (6/13 vs. 1/16, P =0.019). Patients who underwent surgery were more likely to have lobar and segmental bronchial involvement (13/13 vs. 9/16, P =0.007). A total of 15 patients underwent mNGS, 14 (93.3%) had positive results. Performing metagenomic next generation sequencing for diagnosis shortened the time from disease onset to diagnosis (log-rank P =0.014). Conclusion: Metagenomic next-generation sequencing aided early diagnosis. The patients who underwent surgery included unilateral multiple lesions and visualisation of endobronchial abnormalities on lobar or segmental bronchus in unilateral lung.

Background: To evaluate and compare the long-term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. 'Long-term' is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs)., Methods: This systematic review and model-based network meta-analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs. Patients with NTG were selected based on strict inclusion/exclusion criteria, with randomsation procedures and masking as reported in the individual trials. Eight different medications were compared, including prostaglandin analogues, beta-blockers, brimonidine, unoprostone isopropyl, brovincamine, and palmitoylethanolamide (PEA). Notably, PEA is an oral medication, while other drugs are topical agents., Results: Primary outcome is the long-term efficacy of IOP control across medications with different follow-up durations. Among the eight medications, PEA demonstrates the highest efficacy (Surface under the cumulative ranking, SUCRA = 7.46%), followed by two prostaglandin analogues: travoprost (SUCRA = 6.86%) and latanoprost (SUCRA = 6.76%), then two beta-blockers: nipradilol (SUCRA = 4.90%) and timolol (SUCRA = 4.89%). Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy. Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness., Conclusions: This study revealed PEA as a promising agent for long-term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy. The outcomes call for PEA's consideration in clinical practice and highlight the need for further research into its long-term efficacy and safety for NTG., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Transition metal dichalcogenides (TMDs) are 2D materials in which the layers are stacked together by van der Waals forces. Although TMDs are expected to be promising for electronic applications, forming a uniform electrode on them is challenging because of the low adhesion forces between metals and TMDs. This study focuses on improving the quality of metal electrodes by introducing atomic H to create surface defects, using Ni on WS 2 as an example. The detailed effects of H etching and subsequent Ni growth were investigated using scanning tunneling microscopy (STM) and synchrotron-based X-ray photoemission (XPS) techniques. Our studies reveal that introducing point defects of ∼3.05 × 10 11 cm -2 on the WS 2 surface, results in a significant shift in Ni growth from the Volmer-Weber to a near Frank-van der Merwe mode. The origin of the change is the bond formation between the Ni and W atoms, which is expected to realize ohmic contact. The optimization of metal-TMD interfaces offers valuable insights for advanced applications.

Racial and ethnic minorities bear a disproportionate burden of type 2 diabetes (T2D) and its complications, with social determinants of health (SDoH) recognized as key drivers of these disparities. Implementing efficient and effective social needs management strategies is crucial. We propose a machine learning analytic pipeline to calculate the individualized polysocial risk score (iPsRS), which can identify T2D patients at high social risk for hospitalization, incorporating explainable AI techniques and algorithmic fairness optimization. We use electronic health records (EHR) data from T2D patients in the University of Florida Health Integrated Data Repository, incorporating both contextual SDoH (e.g., neighborhood deprivation) and person-level SDoH (e.g., housing instability). After fairness optimization across racial and ethnic groups, the iPsRS achieved a C statistic of 0.71 in predicting 1-year hospitalization. Our iPsRS can fairly and accurately screen patients with T2D who are at increased social risk for hospitalization., (© 2024. The Author(s).)

Two new species, Chlorocilliumsinense and Calcarisporiumguizhouense , isolated from a spider and fruiting body of Cordyceps sp., are introduced. Morphological comparisons and phylogenetic analyses based on multigene datasets (ITS+LSU+ RPB2 + tef -1alpha) support the establishment of the new species. A combined dataset of ITS, LSU, RPB2 , and tef -1alpha showed the taxonomic placement of Chlorocillium in Clavicipitaceae for the first time. Pseudometarhizium is regarded as a synonym of Chlorocillium and two Pseudometarhizium species are transferred into the latter based on the phylogenetic analysis and morphological characteristics., Competing Interests: The authors have declared that no competing interests exist., (Wan-Hao Chen, Dan Li, Jian-Dong Liang, Xiu-Xiu Ren, Jie-Hong Zhao, Yan-Feng Han.)

Myricetin (1), Quercetin (2), Kaempferol (3) and Kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO-LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV-vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p-π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator-activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Water pollution has caused problems in coastal areas, rivers, lakes, and other important water sources around the world as a result of inappropriate waste management. Meanwhile, these pollutants are harmful to humans and aquatic life. Textile dye effluent methyl orange (MO) was used in this work for dye degradation studies employing nanocomposites. As a result, the importance of synthesizing pure ZnO and Co 3 O 4 nanoparticles with composites of ZnCo 2 O 4 (zinc cobaltite) nanorods in three various proportions (90:10, 75:25, and 50:50) is emphasized in this study. Many advanced approaches were used to assess the various features of these materials, including size and shape. Fourier transform infrared (FT-IR) spectroscopy was used to determine the vibrational modes of the materials. The absorption measurements were then carried out using UV-vis spectroscopic techniques, and the photocatalytic breakdown of MO was done under visible light irradiation. The findings revealed that pure materials were inadequate for visible light activity, resulting in decreased degradation efficiencies. Spinel cobaltite structures have potential degradation efficiency under visible light, while ZnCo 2 O 4 (50:50) catalyst has superior degradation efficiency of 59.8% over MO. The crystallite size, morphology, functional group, absorption wavelength, and band gap all play important roles in enhancing the material's photocatalytic activity under visible light. Meanwhile, ZnCo 2 O 4 spinel structures are crucial for increasing charge carriers and reducing electron-hole recombination. As a result, zinc cobaltite minerals are widely used in industrial dye degradation applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epidemiological and preclinical studies have indicated a factual association between gut microbiota dysbiosis and high incidence of colitis. Dietary polysaccharides can specifically shift the composition of gut microbiome response to colitis. Here we validated the preventive role of polysaccharides from Pericarpium Citri Reticulatae 'Chachiensis' (PCRCP), a well-known traditional Chinese medicine, in colitis induced by dextrose sodium sulfate (DSS) in both rats and mice. We found that treatment with PCRCP not only significantly reduced DSS-induced colitis via down-regulating colonic inflammatory signaling pathways including PI3K-Akt, NLRs and NF-κB, but also enhanced colonic barrier integrity in rats. These protective activities of PCRCP against DSS-induced injuries in rats were in part due to the modulation of the gut microbiota revealed by both broad-spectrum antibiotic (ABX)-deleted bacterial and non-oral treatments. Furthermore, the improvement of PCRCP on colitis was impaired by intestinal neomycin-sensitive bacteria in DSS-exposed mice. Specifically, in vivo and in vitro treatment with PCRCP led to a highly sensible enrichment in the gut commensal Parabacteroides goldsteinii. Administration of Parabacteroides goldsteinii significantly alleviated typical symptoms of colitis and suppressed the activation of PI3K-Akt-involved inflammatory response in DSS-exposed mice. The anti-colitic effects of Parabacteroides goldsteinii were abolished after the activation of PI3K-Akt signaling pathway by lipopolysaccharide treatment in mice exposed to DSS. This study provides new insights into an anti-colitic mechanism driven by PCRCP and highlights the potential prebiotic of Parabacteroides goldsteinii for the prevention of ulcerative colitis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Hypoxia and lactate-overexpressed tumor microenvironment always lead to poor therapeutic effect of radiotherapy. Here, platinum nanoparticles-embellished hafnium metal-organic framework (Hf-MOF-Pt NPs) were elaborately integrated with Shewanella oneidensis MR-1 (SO) to construct an engineered biohybrid platform (SO@Hf-MOF-Pt) for enhancing radiotherapy. Benefiting from the tumor-targeting and metabolic respiration characteristics of SO, SO@Hf-MOF-Pt could enrich in tumor sites and continuously metabolize the overexpressed lactate, which specifically downregulated the expression of hypoxia-inducible factor (HIF-1α), thereby relieving the radiosuppressive tumor microenvironment to some extent. Moreover, SO@Hf-MOF-Pt would react with tumor-overexpressed hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ) and further inhibit the expression of HIF-1α, resulting in the downregulation of lactate dehydrogenase (LDHA) and subsequently reducing the lactate production. Under these multiple cascaded effects, the radiosuppressive tumor microenvironment was significantly reshaped, thus potentiating the radiosentization of SO@Hf-MOF-Pt and remarkably amplifying the therapeutic outcomes of radiotherapy. The designed biohybrid SO@Hf-MOF-Pt represented promising prospects in sensitizing radiotherapy via bacterium-based metabolic regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Drug-induced liver injury (DILI) is one of the most common liver diseases. The crucial role of lipid droplets (LDs) and hydrogen peroxide (H 2 O 2 ), two important biomarkers in the pathophysiology of DILI, has spurred considerable efforts to accurately visualize H 2 O 2 and LDs for elucidating their functions in the progression of DILI. However, construction of a single fluorescent probe that is able to simultaneously image H 2 O 2 and LDs dynamics remains to be a challenging task. Therefore, it is of great demand to develop a novel fluorescent probe for tracking the LDs status and H 2 O 2 fluctuation in drug-induced liver injury., Results: We developed an "AIE + ESIPT" fluorescent probe TPEHBT for dual-imaging of LDs and H 2 O 2 during DILI process. TPEHBT displayed greatly enhanced fluorescent response to H 2 O 2 by generating an excited state intramolecular proton transfer (ESIPT) fluorophore TPEHBT-OH with aggregation induced emission (AIE) properties. TPEHBT exhibits high selectivity, sensitivity (LOD = 4.73 nM) and large Stokes shift (320 nm) to H 2 O 2 . Interestingly, TPEHBT can light up LDs with high specificity. The probe was favorably applied in the detection of endogenous and exogenous H 2 O 2 in living cells, and notably in the simultaneous real-time visualization of H 2 O 2 generation and LDs accumulation during DILI process. Moreover, TPEHBT was able to image H 2 O 2 generation in zebrafish animal model with APAP-induced liver injury., Significance: For the first time, probe TPEHBT was applied in the dual-imaging of H 2 O 2 fluctuation and LDs status in APAP-induced liver injury model in vitro and in vivo. The present findings strongly suggest that TPEHBT is a promising tool for monitoring H 2 O 2 and LDs dynamics in DILI progression., Competing Interests: Declaration of competing interest The authors declare no competing financial interest or personal relationships that could inappropriately influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Lupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences., Methods: This qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients' experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants' responses next to the interview questions to support the evaluation of their understanding of the questionnaire items., Results: Overall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience., Conclusions: The symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population., (© 2024. The Author(s).)

Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed by any authors.

This study establishes the first core collection (CC) for Taiwanese Phalaenopsis orchids to preserve genetic diversity and key traits essential for breeding and research, thereby enhancing breeding efficiency without the need for a large maintained parent population. We examined 207 commercial orchid cultivars from ten nurseries, characterized by two phenotypes and genotypic data from eight simple sequence repeat markers. Multiple imputation was applied to estimate missing phenotypes, minimizing potential uncertainties and ensuring the reliability of population structure analysis. Weighted k -means clustering identified seven distinct clusters, highlighting substantial genetic diversity. We proposed a two-step phenotype and genotype strategy and modified genetic distance algorithms to effectively preserve both phenotypic and genetic diversity while retaining key features. Consequently, 22 core accessions were selected, distributed across seven clusters, and representing the orchid germplasm collection. Our evaluation revealed significant diversity preservation, particularly in distinct characteristics and rare features, outperforming other methodologies. Pedigree background analysis further confirmed the representativeness of the CC in maintaining diverse genetic materials. We emphasized the importance of evaluating the CC by detailing the criteria and statistical analyses used to ensure the quality, representativeness, and effectiveness of the selected accessions. This study contributes to orchid breeding, conservation efforts, and sustainable agricultural practices by providing a valuable and comprehensive resource. In conclusion, our research establishes a groundbreaking CC, offering insights into the genetic landscape of Taiwanese Phalaenopsis orchids and highlighting potential advancements in breeding commercially desirable varieties., Competing Interests: Y-YL was employed by Brother Orchid Nursery Co., Ltd., T-CL and T-JL were employed by Wonderorchids Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lai, Chen, Wu, Chen, Chen, Lin, Lin, Lin and Kao.)

Aging, a process of functional decline with the increase of chronological age, is a major risk factor for chronic diseases. Aging shows significant individual differences, which is influenced by both genetic and environmental factors. Accurate measurement of physiological age helps identify individuals with accelerated aging and those at high risk for chronic diseases and mortality, which would promote individual health management and precision medicine for healthy aging. In this paper, we summarize the omics-based aging clocks and discuss their current and future applications.

Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants' baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.

Background: This study investigated the potential associations between neighborhood characteristics, rurality, ethnicity/race, and breast cancer screening outcomes in designated Health Professional Shortage Areas in Central Texas. Limited access to preventive medical care can impact screening rates and outcomes. Previous research on the effects of factors such as rurality, neighborhood socioeconomic status, and education level on cancer prevention behaviors has yielded inconsistent results., Materials and Methods: We analyzed data from a state-funded breast and cervical cancer screening programs for disadvantaged and medically underserved individuals. A mixed-effects logistic regression model was used to assess the impact of residency characteristics (rurality, educational attainment, unemployment, and poverty) on abnormal breast cancer screening outcomes, with individual level (age, ethnicity, race, and education) as control variables., Results: During the studied time, there were 1,139 women screened and 134 abnormal mammograms found. Residency characteristics were not significantly associated with abnormal mammography outcomes at 0.05. However, individual factors are strongly associated with abnormal screening results. Non-Hispanic or Latino white women had increased odds of abnormal clinical outcomes compared with Hispanic or Latino women (OR = 2.03, CI 1.25-3.28; p = 0.004). Additionally, women residing in counties with more than 30% of the population completing college had increased odds of abnormal mammogram outcomes compared with counties with less than 15% college attainment (OR = 2.89, CI 0.99-8.38; p = 0.051)., Conclusions: This study found a significant correlation between area-level educational characteristics and abnormal mammography outcomes. Future research should explore the contextual risk factors influencing breast cancer occurrence and develop targeted interventions for this population., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Background: Our facial skin hosts millions of microorganisms, primarily bacteria, crucial for skin health by maintaining the physical barrier, modulating immune response, and metabolizing bioactive materials. Aging significantly influences the composition and function of the facial microbiome, impacting skin immunity, hydration, and inflammation, highlighting potential avenues for interventions targeting aging-related facial microbes amidst changes in skin physiological properties., Results: We conducted a multi-center and deep sequencing survey to investigate the intricate interplay of aging, skin physio-optical conditions, and facial microbiome. Leveraging a newly-generated dataset of 2737 species-level metagenome-assembled genomes (MAGs), our integrative analysis highlighted aging as the primary driver, influencing both facial microbiome composition and key skin characteristics, including moisture, sebum production, gloss, pH, elasticity, and sensitivity. Further mediation analysis revealed that skin characteristics significantly impacted the microbiome, mostly as a mediator of aging. Utilizing this dataset, we uncovered two consistent cutotypes across sampling cities and identified aging-related microbial MAGs. Additionally, a Facial Aging Index (FAI) was formulated based on the microbiome, uncovering the cutotype-dependent effects of unhealthy lifestyles on skin aging. Finally, we distinguished aging related microbial pathways influenced by lifestyles with cutotype-dependent effect., Conclusions: Together, our findings emphasize aging's central role in facial microbiome dynamics, and support personalized skin microbiome interventions by targeting lifestyle, skin properties, and aging-related microbial factors. Video Abstract., (© 2024. The Author(s).)

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

A pair of epimers of flavonoid alkaloids, with a pyrrolidone moiety, 2 S ,5'' R -eupodoratin A ( 1 ), 2 S ,5'' S -eupodoratin A ( 2 ), together with two known analogues, drahebephin A ( 3 ), drahebephin B ( 4 ), were isolated from the flowers of Chromolaena odorata (L.) R.M.King & H.Rob. Their structures were elucidated on the basis of HR-ESI-MS, 1D/2D NMR spectral analyses. The absolute configuration of compounds ( 1 ) and ( 2 ) was determined by its experimental and calculated electronic circular dichroism (ECD) spectra. All compounds were isolated from the Asteraceae family for the first time. The ABTS · + scavenging activity of compound ( 4 ) reached 93.56% at a concentration of 0.5 mM, while the scavenging capacity of positive control Trolox was 55.94%. In addition, all compounds show moderate antimicrobial activity against Escherichia coli (ATCC, 337304), Staphylococcus aureus (ATCC, 337371) and Candida albicans (ATCC, 186382) with a MIC value of more than 50 µg/mL.

Microplastic contamination has rapidly become a serious environmental issue, threatening marine ecosystems and human health. This review aims to not only understand the distribution, impacts, and transfer mechanisms of microplastic contamination but also to explore potential solutions for mitigating its widespread impact. This review encompasses the categorisation, origins, and worldwide prevalence of microplastics and methodically navigates the complicated structure of microplastics. Understanding the sources of minute plastic particles infiltrating water bodies worldwide is critical for successful removal. The presence and accumulation of microplastics has far reaching negative impacts on various marine creatures, eventually extending its implications to human health. Microplastics are known to affect the metabolic activities and the survival of microbial communities, phytoplankton, zooplankton, and fauna present in marine environments. Moreover, these microplastics cause developmental abnormalities, endocrine disruption, and several metabolic disorders in humans. These microplastics accumulates in aquatic environments through trophic transfer mechanisms and biomagnification, thereby disrupting the delicate balance of these ecosystems. The review also addresses the tactics for minimising the widespread impact of microplastics by suggesting practical alternatives. These include increasing public awareness, fostering international cooperation, developing novel cleanup solutions, and encouraging the use of environment-friendly materials. In conclusion, this review examines the sources and prevalence of microplastic contamination in marine environment, its impacts on living organisms and ecosystems. It also proposes various sustainable strategies to mitigate the problem of microplastics pollution. Also, the current challenges associated with the mitigation of these pollutants have been discussed and addressing these challenges require immediate and collective action for restoring the balance in marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Immunogenic cell death (ICD) often results in the production and accumulation of adenosine (ADO), a byproduct that negatively impacts the therapeutic effect as well as facilitates tumor development and metastasis. Here, an innovative strategy is elaborately developed to effectively activate ICD while avoiding the generation of immunosuppressive adenosine. Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF). Particularly, the designed Bc@AZTF can actively enrich in tumor sites and respond to the acidic tumor microenvironment to offload AZTF nanoparticles, which can consume intracellular ATP (iATP) content and simultaneously inhibit the ATP-adenosine axis to reduce the accumulation of adenosine, thereby alleviating adenosine-mediated immunosuppression and strikingly amplifying ICD effect. Importantly, the synergy of anti-PD-1 (αPD-1) with Bc@AZTF not only establishes a collaborative antitumor immune network to potentiate effective tumoricidal immunity but also activates long-lasting immune memory effects to manage tumor recurrence and rechallenge, presenting a new paradigm for ICD treatment combined with adenosine metabolism., (© 2024 Wiley‐VCH GmbH.)

Hyperalgesic priming, a form of pain plasticity initiated by initial injury, leads to heightened sensitivity to subsequent noxious stimuli, contributing to chronic pain development in animals. While astrocytes play active roles in modulating synaptic transmission in various pain models, their specific involvement in hyperalgesic priming remains elusive. Here, we show that spinal astrocytes are essential for hyperalgesic priming formation in a mouse model of acid-induced muscle pain. We observed spinal astrocyte activation 4 h after initial acid injection, and inhibition of this activation prevented chronic pain development upon subsequent acid injection. Chemogenetic activation of spinal astrocytes mimicked the first acid-induced hyperalgesic priming. We also demonstrated that spinal phosphorylated extracellular regulated kinase (pERK)-positive neurons were mainly vesicular glutamate transporter-2 positive (Vglut2 + ) neurons after the first acid injection, and inhibition of spinal pERK prevented astrocyte activation. Furthermore, pharmacological inhibition of astrocytic glutamate transporters glutamate transporter-1 and glutamate-aspartate transporter abolished the hyperalgesic priming. Collectively, our results suggest that pERK activation in Vglut2 + neurons activate astrocytes through astrocytic glutamate transporters. This process eventually establishes hyperalgesic priming through spinal D-serine. We conclude that spinal astrocytes play a crucial role in the transition from acute to chronic pain., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

The tumor microenvironment (TME) of prostate cancer (PCa) is characterized by high levels of immunosuppressive molecules, including cytokines and chemokines. This creates a hostile immune landscape that impedes effective immune responses. The interleukin-1 (IL-1) receptor antagonist (IL1RN), a key anti-inflammatory molecule, plays a significant role in suppressing IL-1-related immune and inflammatory responses. Our research investigates the oncogenic role of IL1RN in PCa, particularly its interactions with muscarinic acetylcholine receptor 4 (CHRM4), and its involvement in driving immunosuppressive pathways and M2-like macrophage polarization within the PCa TME. We demonstrate that following androgen deprivation therapy (ADT), the IL1RN-CHRM4 interaction in PCa activates the MAPK/AKT signaling pathway. This activation upregulates the transcription factors E2F1 and MYCN, stimulating IL1RN production and creating a positive feedback loop that increases CHRM4 abundance in both PCa cells and M2-like macrophages. This ADT-driven IL1RN/CHRM4 axis significantly enhances immune checkpoint markers associated with neuroendocrine differentiation and treatment-resistant outcomes. Higher serum IL1RN levels are associated with increased disease aggressiveness and M2-like macrophage markers in advanced PCa patients. Additionally, elevated IL1RN levels correlate with better clinical outcomes following immunotherapy. Clinical correlations between IL1RN and CHRM4 expression in advanced PCa patients and neuroendocrine PCa organoid models highlight their potential as therapeutic targets. Our data suggest that targeting the IL1RN/CHRM4 signaling could be a promising strategy for managing PCa progression and enhancing treatment responses., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Vascular calcification is a common vascular lesion associated with high morbidity and mortality from cardiovascular events. Antibiotics can disrupt the gut microbiota (GM) and have been shown to exacerbate or attenuate several human diseases. However, whether antibiotic-induced GM disruption affects vascular calcification remains unclear., Methods: Antibiotic cocktail (ABX) treatment was utilized to test the potential effects of antibiotics on vascular calcification. The effects of antibiotics on GM and serum short-chain fatty acids (SCFAs) in vascular calcification mice were analyzed using 16 S rRNA gene sequencing and targeted metabolomics, respectively. Further, the effects of acetate, propionate and butyrate on vascular calcification were evaluated. Finally, the potential mechanism by which acetate inhibits osteogenic transformation of VSMCs was explored by proteomics., Results: ABX and vancomycin exacerbated vascular calcification. 16 S rRNA gene sequencing and targeted metabolomics analyses showed that ABX and vancomycin treatments resulted in decreased abundance of Bacteroidetes in the fecal microbiota of the mice and decreased serum levels of SCFAs. In addition, supplementation with acetate was found to reduce calcium salt deposition in the aorta of mice and inhibit osteogenic transformation in VSMCs. Finally, using proteomics, we found that the inhibition of osteogenic transformation of VSMCs by acetate may be related to glutathione metabolism and ubiquitin-mediated proteolysis. After adding the glutathione inhibitor Buthionine sulfoximine (BSO) and the ubiquitination inhibitor MG132, we found that the inhibitory effect of acetate on VSMC osteogenic differentiation was weakened by the intervention of BSO, but MG132 had no effect., Conclusion: ABX exacerbates vascular calcification, possibly by depleting the abundance of Bacteroidetes and SCFAs in the intestine. Supplementation with acetate has the potential to alleviate vascular calcification, which may be an important target for future treatment of vascular calcification., (© 2024. The Author(s).)

The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4. Purified equine polyclonal IgG provided protection against Omicron XBB.1.5 virus in the K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based nanoparticle vaccines can rapidly produce a broad and protective sarbecovirus response in the equine model and that equine serum has therapeutic potential against emerging SARS-CoV-2 VoC and diverse sarbecoviruses, presenting a possible alternative or supplement to monoclonal antibody immunotherapies., Competing Interests: W.H.C, A.H., P.V.T., J.L.J., K.M. and M.G.J. are named inventors on provisional patents describing SpFN molecules. S.J.K., V.D., N.L.M., and K.M. are named inventors on provisional patents describing monoclonal antibodies against coronaviruses. M.G.J. is named as an inventor on international patent application WO/2018/081318 and U.S. patents 10,960,070, and 11,964,010 entitled “Prefusion coronavirus spike proteins and their use.” K.M. is a current employee of Pfizer and may, therefore, be a shareholder. A.F., K.Mur., and J.Kau. are former or current employees of B.S.V. The other authors declare no competing interests., (© 2024 The Author(s).)

Background and Objectives : As the global aging population grows, the incidence of thyroidectomy in elderly patients is increasing. This study aimed to evaluate the surgical outcomes of thyroidectomy in patients aged 80 years and older. Materials and Methods : All patients aged 80 years and older who underwent thyroidectomies at our hospital between January 2015 and December 2022 were reviewed in this retrospective cohort study. Collected data consisted of patients' clinical characteristics, functional status, compression symptoms, preoperative assessments, perioperative outcomes, postoperative complications (such as bleeding events, recurrent laryngeal nerve injury, hypocalcemia), pathological findings, readmission, and follow-up outcomes. Results : Seventeen patients were included in this study, with female predominance (82.4%). The mean age was 85.6 ± 4.8 years. Fourteen patients (82.4%) exhibited compression-related symptoms as surgical indications. Based on pathological reports, patients were categorized into benign (12/17, 70.6%) and malignancy (5/17, 29.4%) groups. The benign group had a shorter operation time compared with the malignancy group (164.3 ± 32.0 min vs. 231.0 ± 79.1 min, p = 0.048). No major postoperative complications developed. The median postoperative follow-up duration was 28 months (range: 2-91 months). Thirteen patients (76.5%) were alive at the end of the study period. Conclusions : Despite potential age-related risks, thyroidectomy is feasible for carefully selected patients aged 80 years and older. It provides benefits not only in terms of oncological curative treatment but also in improving the quality of life, such as compressive symptoms and wound condition.

Genetic variations are instrumental for unraveling phage evolution and deciphering their functional implications. Here, we explore the underlying fine-scale genetic variations in the gut phageome, especially structural variations (SVs). By using virome-enriched long-read metagenomic sequencing across 91 individuals, we identified a total of 14,438 nonredundant phage SVs and revealed their prevalence within the human gut phageome. These SVs are mainly enriched in genes involved in recombination, DNA methylation, and antibiotic resistance. Notably, a substantial fraction of phage SV sequences share close homology with bacterial fragments, with most SVs enriched for horizontal gene transfer (HGT) mechanism. Further investigations showed that these SV sequences were genetic exchanged between specific phage-bacteria pairs, particularly between phages and their respective bacterial hosts. Temperate phages exhibit a higher frequency of genetic exchange with bacterial chromosomes and then virulent phages. Collectively, our findings provide insights into the genetic landscape of the human gut phageome.

Pedestrian trajectory prediction is crucial for developing collision avoidance algorithms in autonomous driving systems, aiming to predict the future movement of the detected pedestrians based on their past trajectories. The traditional methods for pedestrian trajectory prediction involve a sequence of tasks, including detection and tracking to gather the historical movement of the observed pedestrians. Consequently, the accuracy of trajectory prediction heavily relies on the accuracy of the detection and tracking models, making it susceptible to their performance. The prior research in trajectory prediction has mainly assessed the model performance using public datasets, which often overlook the errors originating from detection and tracking models. This oversight fails to capture the real-world scenario of inevitable detection and tracking inaccuracies. In this study, we investigate the cumulative effect of errors within integrated detection, tracking, and trajectory prediction pipelines. Through empirical analysis, we examine the errors introduced at each stage of the pipeline and assess their collective impact on the trajectory prediction accuracy. We evaluate these models across various custom datasets collected in Taiwan to provide a comprehensive assessment. Our analysis of the results derived from these integrated pipelines illuminates the significant influence of detection and tracking errors on downstream tasks, such as trajectory prediction and distance estimation.

Background: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma., Methods: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis., Results: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups., Conclusions: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cadmium (Cd) pollution has been a significant concern in heavy metal pollution, prompting plants to adopt various strategies to mitigate its damage. While the response of plants to Cd stress and the impact of exogenous melatonin has received considerable attention, there has been limited focus on the responses of closely related species to these factors. Consequently, our investigation aimed to explore the response of three different species of rape to Cd stress and examine the influence of exogenous melatonin in this scenario. The research findings revealed distinctive responses among the investigated rape species. B. campestris showed the resistance to Cd and exhibited lower Cd absorption and sustained its physiological activity under Cd stress. In contrast, B. juncea accumulated much Cd and increased the amount of anthocyanin to mitigate the Cd-damage. Furthermore, B. napus showed the tolerance to Cd and tended to accumulate Cd in vacuoles under Cd stress, thereby decreasing the Cd damage and leading to higher activity of antioxidant enzymes and photosynthesis. Moreover, the application of exogenous melatonin significantly elevated the melatonin level in plants and mitigated Cd toxicity by promoting the activity of antioxidant enzymes, reducing Cd absorption, enhancing the chelating capacity with Cd, decreasing Cd accumulation in organelles, and reducing its fluidity. Specifically, exogenous melatonin increased the F HAc content in B. campestris, elevated the phytochelatins (PCs) level in B. napus, and stimulated photosynthesis in B. juncea. In summary, the findings underscore the species-specific responses of the three species of rape to both Cd stress and exogenous melatonin, highlighting the potential for tailored mitigation strategies based on the unique characteristics of each species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The objective was to compare simplified pressure insoles integrating different sensor numbers and to identify a promising range of sensor numbers for accurate center of pressure (CoP) measurement. Twelve participants wore a 99-sensor Pedar-X insole (100 Hz) during walking, jogging, and running. Eight simplified layouts were simulated, integrating 3-17 sensors. Concordance correlation coefficients (CCC) and root mean square errors (RMSE) between the original and simplified layouts were calculated for time-series mediolateral (ML) and anteroposterior (AP) CoP. Differences between layouts and between gait types were assessed via ANOVA and Friedman test. Concordance between the original and simplified layouts varied across layouts and gaits (CCC: 0.43-0.98; χ(7)2 ≥ 34.94, p < 0.001). RMSE ML and RMSE AP [mm], respectively, were smaller in jogging (5 ± 2, 15 ± 9) than in walking (8 ± 2, 22 ± 4) and running (7 ± 4, 20 ± 7) (ηp2: 0.70-0.83, p < 0.05). Only layouts with 11+ sensors achieved CCC ≥ 0.80 in all tests across gaits. The 13-sensor layout achieved CCC ≥ 0.95 with 95% confidence, representing the most promising compromise between sensor number and CoP accuracy. Future research may refine sensor placement, suggesting the use of 11-13 sensors. For coaches, therapists, and applied sports scientists, caution is recommended when using insoles with nine or fewer sensors. Consulting task-specific validation results for the intended products is advisable.

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening., (© 2024. The Author(s).)

The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention., Competing Interests: The authors declare that there are no potential conflicts of interest., (© 2024 The Author(s).)

Background: A retrotransposon HORT1 in the promoter of the anthocyanin activator gene PeMYB11, microRNA858 (miR858) that targets PeMYB11, and a repressor PeMYBx have been implicated in pigmentation patterning diversity of harlequin Phalaenopsis orchids. However, the interrelationship among them remains to be elucidated., Results: To understand how these factors interact to generate anthocyanin spots in Phalaenopsis, we successfully developed a mathematical model based on the known reaction-diffusion system to simulate their interplay and refined the conceptual biological model. Intriguingly, the expression of both PeMYBx and PeMYB11 were in phase for purple spot formation, even though they showed adverse effects on anthocyanin accumulations. An increase in the self-activation rate of PeMYB11 resulted in the increased size of purple spots, but no effects on spot fusion. Decreased degradation rate of miR858 in the purple regions, led to disruption of the formation of spotted pigmentation patterning and a full-red pigmentation pattern. Significantly, the reduced miR858 level promotes the fusion of large dark purple dots induced by the solo-LTR of HORT1, eventually generating the purple patches. In addition, the spatially heterogeneous insertion of HORT1 caused by the remnant solo-LTR of HORT1 derived from random homologous unequal recombination of HORT1 in individual cells of floral organs could explain the diverse pigmentation patterning of harlequin Phalaenopsis., Conclusions: This devised model explains how HORT1 and miR858 regulate the formation of the pigmentation patterning and holds great promise for developing efficient and innovative approaches to breeding harlequin Phalaenopsis orchids., (© 2024. The Author(s).)