Cerebral blood flow alterations and host genetic association in individuals with long COVID: A transcriptomic-neuroimaging study.

Neuroimaging studies have indicated that altered cerebral blood flow (CBF) was associated with the long-term symptoms of postacute sequelae of SARS-CoV-2 infection (PASC), also known as "long COVID". COVID-19 and long COVID were found to be strongly associated with host gene expression. Nevertheless, the relationships between altered CBF, clinical symptoms, and gene expression in the central nervous system (CNS) remain unclear in individuals with long COVID. This study aimed to explore the genetic mechanisms of CBF abnormalities in individuals with long COVID by transcriptomic-neuroimaging spatial association. Lower CBF in the left frontal-temporal gyrus was associated with higher fatigue and worse cognition in individuals with long COVID. This CBF pattern was spatially associated with the expression of 2,178 genes, which were enriched in the molecular functions and biological pathways of COVID-19. Our study suggested that lower CBF is associated with persistent clinical symptoms in long COVID individuals, possibly as a consequence of the complex interactions among multiple COVID-19-related genes, which contributes to our understanding of the impact of adverse CNS outcomes and the trajectory of development to long COVID.

Response Characteristics and Community Assembly Mechanisms of nirS-Type Denitrifiers in the Alpine Wetland under Simulated Precipitation Conditions.

The nitrogen cycling process in alpine wetlands is profoundly affected by precipitation changes, yet the dynamic response mechanism of denitrifiers to long-term precipitation shifts in the alpine wetland of the Qinghai-Tibet Plateau remains enigmatic. Utilizing high-throughput sequencing analysis of nirS-type functional genes, this study delved into the dynamic response mechanism of nirS-type denitrifiers to precipitation changes in the alpine wetland of Qinghai Lake. The findings revealed that nirS-type denitrifiers in the alpine wetland of Qinghai Lake were primarily Proteobacteria, and Alpha diversity exhibited a negative correlation with the precipitation gradient, with deterministic processes predominating in the community assembly of denitrifying microbes. A 50% increase in rainfall shifted the community assembly process of denitrifiers from deterministic to stochastic. Dominant microflora at the genus level responded significantly to precipitation changes, with aerobic bacteria comprising the majority of differentially abundant taxa (55.56%). As precipitation increased, the complexity of the microbial interaction network decreased, and a 25% reduction in precipitation notably elevated the relative abundance of three key functional groups: chemoheterotrophic, aerobic chemoheterotrophic, and nitrogen fixation. Precipitation notably emerged as the primary regulator of nirS-type denitrifiers in the alpine wetland of Qinghai Lake, accounting for 51% of the variation in community composition. In summary, this study offers a fresh perspective for investigating the ecological processes of nitrogen cycling in alpine ecosystems by examining the diversity and community composition of nirS-type denitrifiers in response to precipitation changes.

Comparative transcriptome analysis of two pomelo accessions with different parthenocarpic ability provides insight into the molecular mechanisms of parthenocarpy in pomelo (Citrus grandis).

Parthenocarpy is an important way for seedless fruit production in citrus. However, the molecular mechanism(s) of parthenocarpy in pomelo is still unknown. Our initial study found significantly different parthenocarpic abilities in Guanximiyou (G) and Shatianyou (S) pomelo following emasculation, and an endogenous hormone content assay revealed that indole-3-acetic acid (IAA), gibberellic acid (GA3) and zeatin (ZT) jointly promoted fruit expansion and cell division in parthenocarpic pomelo (G pomelo). To unravel the underlying molecular mechanism(s), we conducted the first transcriptome analysis on the two pomelo accessions at these two critical stages: the fruit initiation stage and the rapid expansion stage, in order to identify genes associated with parthenocarpy. This analysis yielded approximately 7.86 Gb of high-quality reads, and the subsequent de novo assembly resulted in the identification of 5,792 DEGs (Differentially Expressed Genes). Among these, a range of transcription factor families such as CgERF, CgC2H2, CgbHLH, CgNAC and CgMYB, along with genes like CgLAX2, CgGH3.6 and CgGH3, emerged as potential candidates contributing to pomelo parthenocarpy, as confirmed by qRT-PCR analysis. The present study provides comprehensive transcriptomic profiles of both parthenocarpic and non-parthenocarpic pomelos, reveals several metabolic pathways linked to parthenocarpy, and highlights the significant role of plant hormones in its regulation. These findings deepen our understanding of the molecular mechanisms underlying parthenocarpy in pomelo.

Quasi-Solid-State Electrolyte Induced by Metallic MoS2 for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are a promising high-energy-density technology for next-generation energy storage but suffer from an inadequate lifespan. The poor cycle life of Li-S batteries stems from their commonly adopted catholyte-mediated operating mechanism, where the shuttling of dissolved polysulfides results in active material loss on the sulfur cathode and surface corrosion on the lithium anode. Here, we report in situ formation of a quasi-solid-state electrolyte (QSSE) on the metallic 1T phase molybdenum disulfide (MoS2) host that extends the lifetime of Li-S batteries. We find that the metallic 1T phase MoS2 host is able to initiate the ring-opening polymerization of 1,3-dioxolane (DOL), forming an integrated QSSE inside batteries. Nuclear magnetic resonance analysis reveals that the QSSE consists of ∼13% liquid DOL in a solid polymer matrix. The QSSE efficiently mediates sulfur redox reactions through dissolution-conversion chemistry while simultaneously suppressing polysulfide shuttling. Therefore, while ensuring high sulfur utilization, it avoids degradation of both electrodes, as well as the concomitant electrolyte consumption, leading to enhanced cycling stability. Under a practical lean electrolyte condition (electrolyte-to-sulfur ratio = 2 µL mg-1), Li-S pouch cell batteries with the QSSE demonstrate a capacity retention of 80.7% after 200 cycles, much superior to conventional liquid electrolyte cells that fail within 70 cycles. The QSSE also enables Li-S pouch cell batteries to operate across a wider temperature range (5 to 45 °C), together with improved safety under mechanical damage.

Additive-free Absorbable Keratin Sponge With Procoagulant Activity for Noncompressible Hemostasis.

The development of a natural, additive-free, absorbable sponge with procoagulant activity for noncompressible hemostasis remains a challenging task. In this study, we extracted high molecular weight keratin (HK) from human hair and transformed it into a hemostatic sponge with a well-interconnected pore structure using a foaming technique, freeze-drying, and oxidation cross-linking. By controlling the cross-linking degree, the resulting sponge demonstrated excellent liquid absorption ability, shape recovery characteristics, and robust mechanical properties. The HK10 sponge exhibited rapid liquid absorption, expanding up to 600% within 5 s. Moreover, the HK sponge showed superior platelet activation and blood cell adhesion capabilities. In SD rat liver defect models, the sponges demonstrated excellent hemostatic performance by sealing the wound and expediting coagulation, reducing the hemostatic time from 825 to 297 s. Furthermore, HK sponges have excellent biosafety, positioning them as a promising absorbable sponge with the potential for the treatment of noncompressible hemostasis.

Response Mechanism of cbbM Carbon Sequestration Microbial Community Characteristics in Different Wetland Types in Qinghai Lake.

Carbon-sequestering microorganisms play an important role in the carbon cycle of wetland ecosystems. However, the response mechanism of carbon-sequestering microbial communities to wetland type changes and their relationship with soil carbon remain unclear. To explore these differences and identify the main influencing factors, this study selected marsh wetlands, river wetlands and lakeside wetlands around Qinghai Lake as research subjects. High-throughput sequencing was employed to analyze the functional gene cbbM of carbon-sequestering microorganisms. The results revealed that the alpha diversity of cbbM carbon-sequestering microorganisms mirrored the trend in total carbon content, with the highest diversity observed in marsh wetlands and the lowest in lakeside wetlands. The dominant bacterial phylum was Proteobacteria, with prevalent genera including Thiothrix, Acidithiobacillus, and Thiodictyon. Acidithiobacillus served as a biomarker in lakeside wetlands, while two other genera were indicative of marsh wetlands. The hierarchical partitioning analysis indicated that the diversity of cbbM carbon-fixing microorganisms was primarily influenced by the total nitrogen content, while the community structure was significantly affected by the soil total carbon content. Moreover, an increased soil temperature and humidity were found to favor the carbon fixation processes of Thiomicrospira, Thiomonas, Polaromonas, and Acidithiobacillus. In summary, changes in wetland types seriously affected the characteristics of cbbM carbon sequestration in microbial communities, and a warm and humid climate may be conducive to wetland carbon sequestration.

Circulating long noncoding RNA, Zfpm2-As1, and XIST based on medical data analysis are potential plasma biomarkers for gastric cancer diagnosis.

BACKGROUND: Long noncoding RNAs (lncRNAs) participate in diseases, especially tumorigenesis, including gastric cancer (GC). Although lncRNAs in GC tissues have been extensively studied in previous research, the possible significance of circulating lncRNAs in diagnosing GC is still unknown. OBJECTIVE: The present work investigated lncRNAs ZFPM2-AS1 and XIST with high expression in GC tissues proved as potential plasma biomarkers from 20 early GC cases, 100 GC cases, and 90 normal subjects. METHODS: The possible correlation between ZFPM2-AS1 and XIST expression levels was analyzed with general characteristics and clinicopathological features. The performance in diagnosis was assessed according to receiver operating characteristic (ROC) analysis. RESULTS: According to the results, XIST and ZFPM2-AS1 expression remarkably increased within GC plasma relative to normal subjects (P< 0.01); besides, lncRNA XIST expression after surgery had a tendency of downregulation compared with preoperative levels (P< 0.05). Moreover, the area under ROC curve (AUC) values were 0.62 for ZFPM2-AS1 and 0.68 for XIST, while the pooled AUC value of CA-724 and two lncRNAs was 0.751. CONCLUSION: Circulating lncRNAs ZFPM2-AS1 and XIST can serve as the candidate plasma biomarkers used to diagnose GC.

Vertical differentiation drives the changes in the main microflora and metabolites of carbon and nitrogen cycling in the early freeze-thaw period in the Qinghai Lake Basin.

Global climate change has altered the frequency of soil freeze-thaw cycles, but the response of soil microorganisms to different elevation gradients during the early freeze-thaw period remains unclear. So far, the influence of the altitudinal gradient on the microbial community and metabolic characteristics in the early freeze-thaw period of the Qinghai Lake Basin remains unclear. To this end, we collected soil at different elevations in the early freeze-thaw period of the Qinghai Lake Basin and investigated the influence of the elevation gradient on soil microbial community characteristics and soil metabolic processes as well as the corresponding environmental driving mechanism by high-throughput sequencing and LC-MS (Liquid Chromatograph-Mass Spectrometer) nontargeted metabolite determination. The results showed that Proteobacteria were the dominant microflora in the Qinghai Lake Basin. The dominant phyla associated with carbon and nitrogen are Proteobacteria and Firmicutes, both of which are significantly affected by elevation. The soil physicochemical factors jointly affected the soil microbial communities and metabolism. Total phosphorus nitrate nitrogen and pH were the main driving factors of the microbial community, and metabolites were sensitive to changes in chemical factors. In short, the microbial community structure and function, soil physicochemical factors and soil metabolic processes were significantly affected by the altitudinal gradient in the early freeze-thaw period, while the microbial community diversity showed no significant response to the altitudinal gradient. Additionally, a high potassium content in the soil may promote the growth and reproduction of bacteria associated with carbon and nitrogen cycling, as well as the production of metabolites.

The Piezocatalytic Degradation of Sulfadiazine by Lanthanum-Doped Barium Titanate.

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol-gel-hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min-1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

Temporal and topological properties of dynamic networks reflect disability in patients with neuromyelitis optica spectrum disorders.

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD.

First Report of Meloidogyne enterolobii Infecting Yellow pitaya (Selenicereus megalanthus) in China.

Yellow pitaya, Selenicereus megalanthus, is a night-blooming, climbing cacti of tropical origin, which has received increasing attention for its potential as a new exotic fruit crop (Lichtenzveig et al. 2000). The crop is grown extensively in Hainan Province, China (3000 ha). In October 2021, a survey was conducted on a farm located in Changjiang (19°21'4″N, 108°47'2″S), Hainan Province, China. Some yellow pitaya plants were found that were stunted and chlorotic, with abnormally thin stems (Fig. 1B), and no symptoms on healthy plants (Fig. 1A). Dead plants were also observed. Many galls and females with egg masses were observed on roots (Figs. 1C & 1D). This is typical of root-knot nematode (RKN) infections, and the incidence of infection was 36.7%. Meloidogyne sp. females and egg masses were dissected from roots of the infected plants. The perineal pattern of females (n= 5) was round to oval-shaped with a high dorsal arch (Figs. 1I & 1J). Second-stage juveniles (J2s) had truncated lips (Figs. 1E & 1F) and long-conical tails with bluntly rounded tips (Figs. 1G & 1H). The J2s body length (n= 24) averaged 416.79 µm (349.21 to 472.76 µm) with a mean width of 15.36 µm (12.47 to 17.52 µm); mean stylet length was 11.16 µm (10.10 to 13.23 µm); tail length averaged 53.73 µm (43.46 to 65.90 µm). The morphological characteristics matched the original description of M. enterolobii (Yang and Eisenback 1983). Males were not found. Genomic DNA was extracted from eight single J2s, and the mitochondrial (mtDNA) region between COII and 16S rRNA gene was amplified with primers C2F3/1108 (Powers and Harris 1993). A 652-bp DNA fragment was obtained, for which the sequence (GenBank accession no. OP122499) was 100% identical to the sequences of M. enterolobii isolates from China（MN269947）and the USA (MN809527). Furthermore, species identification was also confirmed using M. enterolobii specific primers Me-F/Me-R. An amplicon size of ∼230 bp was obtained, which is consistent with those previously reported for M. enterolobii (Fig. 2) (Long et al. 2006). Therefore, this population was identified as M. enterolobii based on morphological and molecular characteristics. Pathogenicity tests were performed in the greenhouse at 26℃ and 80% relative humidity with a 14-h/10-h light/dark photoperiod. Ten RKN-free S. megalanthus seedlings were transplanted into pots containing sterilized soil. After 3 weeks, the roots of 5 plants were inoculated with 3,000 eggs and J2s of M. enterolobii per plant. Five uninoculated plants were used as control plants. After 2 months, no galling or symptoms were observed on the control plants. All inoculated plants had galled roots similar to those observed in the field. Females and egg masses were obtained by dissecting galls. The nematode reproduction factor (RF= final population/initial population) was 1.9. Adult females (n= 5) dissected from inoculated plants were identified as M. enterolobii with sequence-specific primers Me-F/Me-R, thus confirming pathogenicity. The pathogenicity test was carried out twice with similar results. M. enterolobii is one of the most damaging species of RKN, due to its wide host range, high level of pathogenicity, and ability to develop and reproduce on several crops with resistance genes to other RKN (Castagnone-Sereno 2012). To our knowledge, this is the first report of S. megalanthus (yellow pitaya) as a host of M. enterolobii in China. Further studies are needed to develop and evaluate integrated management strategies.

Unifying Fourteen Post-Hoc Attribution Methods With Taylor Interactions.

Various attribution methods have been developed to explain deep neural networks (DNNs) by inferring the attribution/importance/contribution score of each input variable to the final output. However, existing attribution methods are often built upon different heuristics. There remains a lack of a unified theoretical understanding of why these methods are effective and how they are related. Furthermore, there is still no universally accepted criterion to compare whether one attribution method is preferable over another. In this paper, we resort to Taylor interactions and for the first time, we discover that fourteen existing attribution methods, which define attributions based on fully different heuristics, actually share the same core mechanism. Specifically, we prove that attribution scores of input variables estimated by the fourteen attribution methods can all be mathematically reformulated as a weighted allocation of two typical types of effects, i.e., independent effects of each input variable and interaction effects between input variables. The essential difference among these attribution methods lies in the weights of allocating different effects. Inspired by these insights, we propose three principles for fairly allocating the effects, which serve as new criteria to evaluate the faithfulness of attribution methods. In summary, this study can be considered as a new unified perspective to revisit fourteen attribution methods, which theoretically clarifies essential similarities and differences among these methods. Besides, the proposed new principles enable people to make a direct and fair comparison among different methods under the unified perspective.

Molecularly imprinted solid-phase extraction combined with non-ionic hydrophobic deep eutectic solvents dispersed liquid-liquid microextraction for efficient enrichment and determination of the estrogens in serum samples.

Hormonal drugs in biological samples are usually in low concentration and highly intrusive. It is of great significance to enhance the sensitivity and specificity of the detection process of hormone drugs in biological samples by utilizing appropriate sample pretreatment methods for the detection of hormone drugs. In this study, a sample pretreatment method was developed to effectively enrich estrogens in serum samples by combining molecularly imprinted solid-phase extraction, which has high specificity, and non-ionic hydrophobic deep eutectic solvent-dispersive liquid-liquid microextraction, which has a high enrichment ability. The theoretical basis for the effective enrichment of estrogens by non-ionic hydrophobic deep eutectic solvent was also computed by simulation. The results showed that the combination of molecularly imprinted solid-phase extraction and deep eutectic solvent-dispersive liquid-liquid microextraction could improve the sensitivity of HPLC by 33∼125 folds, and at the same time effectively reduce the interference. In addition, the non-ionic hydrophobic deep eutectic solvent has a relatively low solvation energy for estrogen and possesses a surface charge similar to that of estrogen, and thus can effectively enrich estrogen. The study provides ideas and methods for the extraction and determination of low-concentration drugs in biological samples and also provides a theoretical basis for the application of non-ionic hydrophobic deep eutectic solvent extraction.

Traditional Chinese Medicine formula, Sanwujiao granule, attenuates ischemic stroke by promoting angiogenesis through early administration.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke (IS) is one of the most lethal diseases with the insufficient pharmacology therapeutic approach. Sanwujiao granule (SW) is widely used for IS in China with little known about its underlying mechanism. AIM OF THE STUDY: To investigate the characteristics of therapeutic effects and potential mechanisms of SW against IS. MATERIALS AND METHODS: The fingerprint of SW was applied by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Three different drug treatment strategies, including prophylactic administration, early administration and delayed administration, were applied in rats' permanent middle cerebral occlusion (pMCAO) model. The Garcia neurological deficit test, adhesive removal test, rotarod test, TTC and TUNEL staining were performed to evaluate the pathological changes. The transcriptomic analysis was used to predict the potential mechanism of SW. The vascular deficiency model of Tg(kdrl:eGFP) zebrafish larvae and oxygen-glucose deprivation model on bEnd.3 cells were used to verify SW's pharmacological effect. qRT-PCR, immunofluorescent staining and Western Blot were applied to detect the expression of genes and proteins. The network pharmacology approach was applied to discover the potential bioactive compounds in SW that contribute to its pharmacological effect. RESULTS: SW early and delayed administration attenuated cerebral infarction, neurological deficit and cell apoptosis. The transcriptomic analysis revealed that SW activated angiogenesis-associated biological processes specifically by early administration. CD31 immunofluorescent staining further confirmed the microvessel intensity in peri-infarct regions was significantly elevated after SW early treatment. Additionally, on the vascular deficiency model of zebrafish larvae, SW showed the angiogenesis effect. Next, the cell migration and tube formation were also observed in the bEnd.3 cells with the oxygen-glucose deprivation induced cell injury. It's worth noting that both mRNA and protein levels of angiogenesis factor, insulin-like growth factor 1, were significantly elevated in the pMCAO rats' brains treated with SW. The network pharmacology approach was applied and chasmanine, karacoline, talatisamine, etc. were probably the main active compounds of SW in IS treatment as they affected the angiogenesis-associated targets. CONCLUSIONS: These results demonstrate that SW plays a critical role in anti-IS via promoting angiogenesis through early administration, indicating that SW is a candidate herbal complex for further investigation in treating IS in the clinical.

[Screening and activity analysis of nanobodies against lymphocyte activation gene-3(LAG-3)].

Objective To generate the phage display nanobody library immunized by lymphocyte-activation gene 3 (LAG-3) and to validate the functional activity of obtained anti-LAG-3 nanobodies. Methods The peripheral blood cDNA library was isolated from the adult llama which was immunized by human LAG-3 protein. The nanobodies sequences were obtained by nested PCR and cloned into the phagemid vector pComb3XSS, then transformed into Escherichia coli XL1-Blue cells for library generation and quality analysis. Anti-LAG-3 specific nanobodies were screened by phage display and sequenced by next-generation sequencing. Nanobodies were cloned into pET-22b (+) vector and Escherichia coli BL21 (DE3) cells were used for protein expression. The proteins were purified by using the Prism A column, then HPLC-MS, ELISA, Western blot, and surface plasmon resonance technology (SPR) were performed to characterize the nanobodies. Results The library capacity of the nanobody phage immune library with great diversity was 7.20×108 CFU/mL. After four rounds of biopanning, three individual nanobodies with distinct amino acid sequences VHH-L1-3, VHH-L3-2 and VHH-L13-2 were picked. The purity of the purified nanobodies was more than 95%. All of these three nanobodies exhibited high binding affinities with recombinant human LAG-3 specifically, among which the KD value of VHH-L13-2 was 3.971×10-9 mol/L. VHH-L13-2 exhibited the inhibitory effects on the association of LAG-3 and its ligand FGL-1, and the half maximal inhibitory concentration (IC50) value was 15.58 nmol/L. Conclusion The anti-LAG-3 phage display nanobody library is generated successfully. The anti-LAG-3 nanobodies possess high specificity and binding affinity and exhibit the inhibitory effects on the association of LAG-3 and its ligand.

Functionalized Fe-Doped Carbon Dots Exhibiting Dual Glutathione Consumption to Amplify Ferroptosis for Enhanced Cancer Therapy.

Nonapoptotic ferroptosis is a promising cancer treatment which offers a solution to the multidrug resistance of conventional apoptosis-induced programmed cancer cell death therapies. Reducing intracellular glutathione (GSH) is essential for inducing excess ROS and has been considered a crucial process to trigger ferroptosis. However, treatments reducing GSH alone have not produced satisfactory effects due to their restricted target. In this regard, FeCDs (Fe3+-modified l-histidine -sourced carbon dots) with dual GSH-consumption capabilities were constructed to engineer ferroptosis by self-amplifying intratumoral oxidative stress. Carbon dots have the ability to consume GSH, and the introduction of Fe3+ can amplify the GSH-consuming ability of CDs, reacting with excess H2O2 in the tumor microenvironment to generate highly oxidized •OH. This is a novel strategy through synergistic self-amplification therapy combining Fe3+ and CDs with GSH-consuming activity. The acid-triggered degradation material (FeCDs@PAE-PEG) was prepared by encapsulating FeCDs in an oil-in-water manner. Compared with other ferroptosis-triggering nanoparticles, the established FeCDs@PAE-PEG is targeted and significantly enhances the consumption efficiency of GSH and accumulation of excess iron without the involvement of infrared light and ultrasound. This synergistic strategy exhibits excellent ferroptosis-inducing ability and antitumor efficacy both in vitro and in vivo and offers great potential for clinical translation of ferroptosis.

SARS-CoV-2 Nsp8 suppresses MDA5 antiviral immune responses by impairing TRIM4-mediated K63-linked polyubiquitination.

Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKKα/ß, subsequently leading to IRF3 and NF-κB phosphorylation. However, the specific E3 ubiquitin ligase for MDA5 K63-polyubiquitination has not been well characterized. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral immune agents indicates that SARS-CoV-2 escapes from antiviral immune responses via several unknown mechanisms. Here, we report that SARS-CoV-2 nonstructural protein 8 (nsp8) acts as a suppressor of antiviral innate immune and inflammatory responses to promote infection of SARS-CoV-2. It downregulates the expression of type I interferon, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and TRIM4 and impairing TRIM4-mediated MDA5 K63-linked polyubiquitination. Our findings reveal that nsp8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases.

Hypoconnectivity of the Amygdala in Patients with Low-Back-Related Leg Pain Linked to Individual Mechanical Pain Sensitivity: A Resting-State Functional MRI Study.

Purpose: To explore resting-state functional connectivity (rsFC) of the amygdala in patients with low-back-related leg pain (LBLP). Patients and Methods: For this prospective study, a total of 35 LBLP patients and 30 healthy controls (HCs) were included and underwent functional MRI and clinical assessments. Then, patients with LBLP were divided into acute LBLP (aLBLP) and chronic LBLP (cLBLP) subgroups. We further evaluated the between-group rsFC differences using left and right amygdala seeds in a whole-brain voxel analysis strategy. Finally, we performed correlation analysis between the rsFC values of altered regions and clinical indices. Results: Compared to HCs, hypoconnectivity of the amygdala was observed in LBLP patients (P < 0.01, with correction). The amygdala's rsFC pattern was different between aLBLP and cLBLP patients: decreased the amygdala's FC to the right putamen, to the right paracentral lobule (PCL), or to the right posterior temporal lobe in aLBLP patients, while right amygdala to the bilateral anterior cingulate cortex (ACC) and the left postcentral gyrus (PoCG) in cLBLP patients. Correlation analysis showed that lower rsFC of the left amygdala to the right PCL was correlated with the von Frey filament (vF) test values of the left lumbar (p = 0.025) and right lumbar (p = 0.019) regions, and rsFC of the right amygdala to the left PoCG was correlated with lower vF test values of the left lumbar (p = 0.017), right lumbar spine (p = 0.003); to right PoCG was correlated with calf (p = 0.015); the rsFC of the right amygdala to bilateral ACC was negatively correlated with the pain rating index (p = 0.003). Conclusion: LBLP patients showed amygdala hypoconnectivity, and the altered pattern of amygdala rsFC was different in the acute and chronic phases. Moreover, the amygdala hypoconnectivity was related to individual mechanical sensitivity (vF test) in LBLP patients.

Multifunctional Metasurface Tuning by Liquid Crystals in Three Dimensions.

Optical metasurfaces present remarkable opportunities for manipulating wave propagation in unconventional ways, surpassing the capabilities of traditional optical devices. In this work, we introduce and demonstrate a multifunctional dynamic tuning of dielectric metasurfaces containing liquid crystals (LCs) through an effective three-dimensional (3D) control of the molecular orientation. We theoretically and experimentally study the spectral tuning of the electric and magnetic resonances of dielectric metasurfaces, which was enabled by rotating an external magnetic field in 3D. Our approach allows for the independent control of the electric and magnetic resonances of a metasurface, enabling multifunctional operation. The magnetic field tuning approach eliminates the need for the pre-alignment of LCs and is not limited by a finite set of directions in which the LC molecules can be oriented. Our results open new pathways for realizing dynamically reconfigurable metadevices and observing novel physical effects without the usual limitations imposed by the boundary conditions of LC cells and the external voltage.