The Voltage-Gated Calcium Channel α2δ Subunit in Neuropathic Pain.

Neuropathic pain (NP) is a chronic pain caused by injury or disease of the somatosensory nervous system, or it can be directly caused by disease. It often presents with clinical features like spontaneous pain, hyperalgesia, and dysesthesia. At present, voltage-gated calcium ion channels (VGCCs) are known to be closely related to the development of NP, especially the α2δ subunit. The α2δ subunit is a regulatory subunit of VGCCs. It exists mainly in the brain and peripheral nervous system, especially in nerve cells, and it plays a crucial part in regulating presynaptic and postsynaptic functions. Furthermore, the α2δ subunit influences neuronal excitation and pain signaling by promoting its expression and localization through binding to VGCC-related subunits. The α2δ subunit is widely used in the management of NP as a target of antiepileptic drugs gabapentin and pregabalin. Although drug therapy is one of the treatments for NP, its clinical application is limited due to the adverse reactions caused by drug therapy. Therefore, further research on the therapeutic target α2δ subunit is needed, and attempts are made to obtain an effective treatment for relieving NP without side effects. This review describes the current associated knowledge on the function of the α2δ subunit in perceiving and modulating NP.

A leaf age-dependent light use efficiency model for remote sensing the gross primary productivity seasonality over pantropical evergreen broadleaved forests.

Tropical and subtropical evergreen broadleaved forests (TEFs) contribute more than one-third of terrestrial gross primary productivity (GPP). However, the continental-scale leaf phenology-photosynthesis nexus over TEFs is still poorly understood to date. This knowledge gap hinders most light use efficiency (LUE) models from accurately simulating the GPP seasonality in TEFs. Leaf age is the crucial plant trait to link the dynamics of leaf phenology with GPP seasonality. Thus, here we incorporated the seasonal leaf area index of different leaf age cohorts into a widely used LUE model (i.e., EC-LUE) and proposed a novel leaf age-dependent LUE model (denoted as LA-LUE model). At the site level, the LA-LUE model (average R2 = .59, average root-mean-square error [RMSE] = 1.23 gC m-2 day-1) performs better than the EC-LUE model in simulating the GPP seasonality across the nine TEFs sites (average R2 = .18; average RMSE = 1.87 gC m-2 day-1). At the continental scale, the monthly GPP estimates from the LA-LUE model are consistent with FLUXCOM GPP data (R2 = .80; average RMSE = 1.74 gC m-2 day-1), and satellite-based GPP data retrieved from the global Orbiting Carbon Observatory-2 (OCO-2) based solar-induced chlorophyll fluorescence (SIF) product (GOSIF) (R2 = .64; average RMSE = 1.90 gC m-2 day-1) and the reconstructed TROPOspheric Monitoring Instrument SIF dataset using machine learning algorithms (RTSIF) (R2 = .78; average RMSE = 1.88 gC m-2 day-1). Typically, the estimated monthly GPP not only successfully represents the unimodal GPP seasonality near the Tropics of Cancer and Capricorn, but also captures well the bimodal GPP seasonality near the Equator. Overall, this study for the first time integrates the leaf age information into the satellite-based LUE model and provides a feasible implementation for mapping the continental-scale GPP seasonality over the entire TEFs.

Characterizing Biphoton Spatial Wave Function Dynamics with Quantum Wavefront Sensing.

With an extremely high dimensionality, the spatial degree of freedom of entangled photons is a key tool for quantum foundation and applied quantum techniques. To fully utilize the feature, the essential task is to experimentally characterize the multiphoton spatial wave function including the entangled amplitude and phase information at different evolutionary stages. However, there is no effective method to measure it. Quantum state tomography is costly, and quantum holography requires additional references. Here, we introduce quantum Shack-Hartmann wavefront sensing to perform efficient and reference-free measurement of the biphoton spatial wave function. The joint probability distribution of photon pairs at the back focal plane of a microlens array is measured and used for amplitude extraction and phase reconstruction. In the experiment, we observe that the biphoton amplitude correlation becomes weak while phase correlation shows up during free-space propagation. Our work is a crucial step in quantum physical and adaptive optics and paves the way for characterizing quantum optical fields with high-order correlations or topological patterns.

Outcomes Using the Optimized Pitch and Language Strategy Versus the Advanced Combination Encoder Strategy in Mandarin-Speaking Cochlear Implant Recipients.

OBJECTIVES: The experimental Optimized Pitch and Language (OPAL) strategy enhances coding of fundamental frequency (F0) information in the temporal envelope of electrical signals delivered to channels of a cochlear implant (CI). Previous studies with OPAL have explored performance on speech and lexical tone perception in Mandarin- and English-speaking CI recipients. However, it was not clear which cues to lexical tone (primary and/or secondary) were used by the Mandarin CI listeners. The primary aim of the present study was to investigate whether OPAL provides improved recognition of Mandarin lexical tones in both quiet and noisy environments compared with the Advanced Combination Encoder (ACE) strategy. A secondary aim was to investigate whether, and to what extent, removal of secondary (duration and intensity envelope) cues to lexical tone affected Mandarin tone perception. DESIGN: Thirty-two CI recipients with an average age of 24 (range 7 to 57) years were enrolled in the study. All recipients had at least 1 year of experience using ACE. Each subject attended two testing sessions, the first to measure baseline performance, and the second to evaluate the effect of strategy after provision of some take-home experience using OPAL. A minimum take-home duration of approximately 4 weeks was prescribed in which subjects were requested to use OPAL as much as possible but were allowed to also use ACE when needed. The evaluation tests included recognition of Mandarin lexical tones in quiet and in noise (signal to noise ratio [SNR] +5 dB) using naturally produced tones and duration/intensity envelope normalized versions of the tones; Mandarin sentence in adaptive noise; Mandarin monosyllabic and disyllabic word in quiet; a subset of Speech, Spatial, and Qualities of hearing questionnaire (SSQ, speech hearing scale); and subjective preference for strategy in quiet and noise. RESULTS: For both the natural and normalized lexical tone tests, mean scores for OPAL were significantly higher than ACE in quiet by 2.7 and 2.9%-points, respectively, and in noise by 7.4 and 7.2%-points, respectively. Monosyllabic word recognition in quiet using OPAL was significantly higher than ACE by approximately 7.5% points. Average SSQ ratings for OPAL were significantly higher than ACE by approximately 0.5 points on a 10-point scale. In quiet conditions, 14 subjects preferred OPAL, 7 expressed a preference for ACE, and 9 reported no preference. Compared with quiet, in noisy situations, there was a stronger preference for OPAL (19 recipients), a similar preference for ACE (7 recipients), while fewer expressed no preference. Average daily take-home use of ACE and OPAL was 4.9 and 7.1 hr, respectively. CONCLUSIONS: For Mandarin-speaking CI recipients, OPAL provided significant improvements to lexical tone perception for natural and normalized tones in quiet and noise, monosyllabic word recognition in quiet, and subjective ratings of speech intelligibility. Subjects accessed both primary and secondary cues to lexical tone for perception in quiet and noise conditions. The benefits of lexical tone recognition were attributed to enhanced F0 rate cues encoded by OPAL, especially in a noisy environment. The OPAL strategy was well accepted by many of the Mandarin-speaking CI recipients.

Gastric metastasis of small cell lung carcinoma: Three case reports and review of literature.

BACKGROUND: Small cell lung carcinoma (SCLC) is highly susceptible to metastasis in the early stages of the disease. However, the stomach is an uncommon site of metastasis in SCLC, and only a few cases of this type of metastasis have been reported. Therefore, SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed. CASE SUMMARY: We report three cases of gastric metastasis from SCLC in this article. The first patient presented primarily with cough, hemoptysis, and epigastric fullness. The other two patients presented primarily with abdominal discomfort, epigastric distension, and pain. All patients underwent gastroscopy and imaging examinations. Meanwhile, the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma. Finally, the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis. The three patients did not receive appropriate treatment and died within a short time. CONCLUSION: Here, we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians' understanding of this disease.

Emerging nanocellulose from agricultural waste: Recent advances in preparation and applications in biobased food packaging.

With the increasing emphasis on sustainability and eco-friendliness, a novel biodegradable packaging materials has received unprecedented attention. Nanocellulose, owing to its high crystallinity, degradability, minimal toxicity, and outstanding biocompatibility, has gained considerable interest in the field of sustainable packaging. This review provided a comprehensive perspective about the recent advances and future development of cellulose nanocrystals (CNCs) and cellulose nanofibers (CNFs). We first introduced the utilization of agricultural waste for nanocellulose production, such as straw, bagasse, fruit byproducts, and shells. Next, we discussed the preparation process of nanocellulose from various agricultural wastes and expounded the advantages and shortcomings of different methods. Subsequently, this review offered an in-depth investigation on the application of nanocellulose in food packaging, especially the function and packaged form of nanocellulose on food preservation. Finally, the safety evaluation of nanocellulose in food packaging is conducted to enlighten and promote the perfection of relevant regulatory documents. In short, this review provided valuable insights for potential research on the biobased materials utilized in future food packaging.

Regioselective Synthesis of Multisubstituted 2,3-Dihydrooxazoles by 1,3-Dithiane Umpolung.

Herein, we report a novel strategy for the regioselective synthesis of aromatic and heteroaromatic 2,3-dihydrooxazoles from 2-alkynyl-1,3-dithianes and nitrones. This method exploits the 1,3-dithiane umpolung, nucleophilic cycloaddition, and rearrangement processes to achieve the rapid assembly of dihydrooxazole molecules. The regioselective method is extremely mild, achieving complete conversion within one min under air at 25 °C with high efficiency.

Inhibition of RHOA activity preserves the survival and hemostasis function of long-term cold stored platelets.

Thrombocytopenic patients require platelet transfusion to prevent and stop hemorrhage. Cold storage of platelets results in complex molecular lesions including changes in membrane microdomains that are recognized by host macrophages and hepatocyte counter-receptors, resulting in phagocytosis and clearance upon transfusion. For this reason, platelets are stored at room temperature, a method that confers increased risk of bacterial contamination. By applying signaling analysis as well as genetic and pharmacological approaches, we identified that the cold induced activation of RHOA GTPase is causal for the major hallmarks of platelet cold storage lesions. RHOA deficiency renders murine platelets insensitive to cold storage induced damage, and pharmacological inhibition by a RHOA activation inhibitor, R-G04, can prevent the cold storage induced lesions. RHOA inhibition prevents myosin activation and clathrin-independent formation and internalization of lipid rafts enriched in active glycosyltransferases as well as abnormal distribution of GpIb. RHOA inhibition further prevents the metabolic reprogramming of cold induced storage lesions and allows the maintenance of glycolytic flux and mitochondrial dependent respiration. Importantly, human platelets transfused in mice after cold storage, in the presence of R-G04 or its more potent enantiomer S-G04, can circulate in vivo at similar levels as room-temperature stored platelets while retaining their hemostatic activity in vivo as assessed by bleeding time correction of aspirin-treated mice. Our studies provide a new mechanism based translational venue to prevent cold storage induced damage useful for human platelet transfusion in thrombocytopenic patients.

Does the establishment of Pilot Free Trade Zones promote international expansion of enterprises? Quasi-natural experimental evidence from China.

Pilot Free Trade Zones (PFTZs) are a crucial new platform for China to build a more open economic system. Existing literature primarily focuses on the 'Bring In' effect of PFTZs, often overlooking the importance of 'Going Out' aspects. To bridge this gap, this paper uses data from China's Shanghai and Shenzhen A-share listed enterprises from 2007 to 2021 and constructs a time-varying difference-in-differences (DID) model to test the impact of establishment of PFTZs on international expansion of enterprises. The study finds that establishment of PFTZs can significantly promote international expansion of enterprises, with a more pronounced effect on the scope of international expansion than on its depth. Mechanism analysis reveals that PFTZs can facilitate international expansion of enterprises by driving digital transformation, enhancing total factor productivity and management efficiency, and alleviating financing constraints. Notably, senior managers with overseas work experience play a crucial role in enhancing this relationship. Further, PFTZs not only have a linkage effect with the Belt and Road Initiative but also a radiation effect on neighboring cities. This study provides an analytical perspective and empirical evidence for evaluating policy effects of PFTZs and offers valuable insights that will enable PFTZ policies to be refined and facilitate successful implementation of the 'Going Out' strategy.

Liraglutide Promotes Diabetic Wound Healing via Myo1c/Dock5.

Non-healing diabetic wounds and ulcer complications, with persistent cell dysfunction and obstructed cellular processes, are leading causes of disability and death in patients with diabetes. Currently, there is a lack of guideline-recommended hypoglycemic drugs in clinical practice, likely due to limited research and unclear mechanisms. In this study, it is demonstrated that liraglutide significantly accelerates wound closure in diabetic mouse models (db/db mice and streptozotocin-induced mice) by improving re-epithelialization, collagen deposition, and extracellular matrix remodeling, and enhancing the proliferation, migration, and adhesion functions of keratinocytes. However, these effects of improved healing by liraglutide are abrogated in dedicator of cytokinesis 5 (Dock5) keratinocyte-specific knockout mice. Mechanistically, liraglutide induces cellular function through stabilization of unconventional myosin 1c (Myo1c). Liraglutide directly binds to Myo1c at arginine 93, enhancing the Myo1c/Dock5 interaction by targeting Dock5 promoter and thus promoting the proliferation, migration, and adhesion of keratinocytes. Therefore, this study provides insights into liraglutide biology and suggests it may be an effective treatment for diabetic patients with wound-healing pathologies.

Research Progress in pathogenesis of connective tissue disease-associated interstitial lung disease from the perspective of pulmonary cells.

The lungs are a principal factor in the increased morbidity and mortality observed in patients with Connective Tissue Disease (CTD), frequently presenting as CTD-associated Interstitial Lung Disease (ILD). Currently, there is a lack of comprehensive descriptions of the pulmonary cells implicated in the development of CTD-ILD. This review leverages the Human Lung Cell Atlas (HLCA) and spatial multi-omics atlases to discuss the advancements in research on the pathogenesis of CTD-ILD from a pulmonary cell perspective. This facilitates a more precise localization of disease sites and a more systematic consideration of disease progression, supporting further mechanistic studies and targeted therapies.

Adaptation of the anammox process for high ammonium photovoltaic wastewater treatment.

Tunnel Oxide Passivating Contacts (TOPcon) battery in the photovoltaic industry generates high ammonium wastewater during the production process, the adaptability of using the anaerobic ammonia oxidation (Anammox) process for photovoltaic wastewater (PVW) treatment is a research hotspot. Based on the analysis of photovoltaic wastewater quality, the effectiveness of nitrogen removal, sludge characteristics and microbial communities were examined. The results showed that when the influent NH4+-N concentration of PVW was lower than 150 mg·L-1, the nitrogen removal efficiency (NRE) was almost 100 %. In addition, the NRE decreased from 74 % sharply to 20 % when the NH4+-N concentration was increased from 175 mg·L-1 to 200 mg·L-1. The extracellular polymeric substances (EPS) content increased with elevated ammonium concentration in the influent, indicating that microorganisms secreted more EPS to resist elevated nitrogen loading. The main functional populations were Candidatus Kuenenia (0-24 %). The influent ammonium concentration is recommended to be < 200 mg·L-1.

Investigating the link between gut microbiome and bone mineral density: The role of genetic factors.

Osteoporosis is a complex metabolic bone disease that severely undermines the quality of life and overall health of the elderly. While previous studies have established a close relationship between gut microbiome and host bone metabolism, the role of genetic factors has received less scrutiny. This research aims to identify potential taxa associated with various bone mineral density states, incorporating assessments of genetic factors. Fecal microbiome profiles from 605 individuals (334 females and 271 males) aged 55-65 from the Taizhou Imaging Study with osteopenia (n = 270, 170 women) or osteoporosis (n = 94, 85 women) or normal (n = 241, 79 women) were determined using shotgun metagenomic sequencing. The linear discriminant analysis was employed to identify differentially enriched taxa. Utilizing the Kyoto Encyclopedia of Genes and Genomes for annotation, functional pathway analysis was conducted to identify differentially metabolic pathways. Polygenic risk score for osteoporosis was estimated to represent genetic susceptibility to osteoporosis, followed by stratification and interaction analyses. Gut flora diversity did not show significant differences among various bone mineral groups. After multivariable adjustment, certain species, such as Clostridium leptum, Fusicatenibacter saccharivorans and Roseburia hominis, were enriched in osteoporosis patients. Statistically significant interactions between the polygenic risk score and taxa Roseburia faecis, Megasphaera elsdenii were observed (P for interaction = 0.005, 0.018, respectively). Stratified analyses revealed a significantly negative association between Roseburia faecis and bone mineral density in the low-genetic-risk group (ß = -0.045, P < 0.05), while Turicimonas muris was positively associated with bone mineral density in the high-genetic-risk group (ß = 4.177, P < 0.05) after multivariable adjustments. Functional predictions of the gut microbiome indicated an increase in pathways related to structural proteins in high-genetic-risk patients, while low-genetic-risk patients exhibited enrichment in enzyme-related pathways. This study emphasizes the association between gut microbes and bone mass, offering new insights into the interaction between genetic background and gut microbiome.

SETDB1 suppresses NK cell-mediated immunosurveillance in acute myeloid leukemia with granulo-monocytic differentiation.

Monocytic acute myeloid leukemia (AML) responds poorly to current treatments, including venetoclax-based therapy. We conducted in vivo and in vitro CRISPR-Cas9 library screenings using a mouse monocytic AML model and identified SETDB1 and its binding partners (ATF7IP and TRIM33) as crucial tumor promoters in vivo. The growth-inhibitory effect of Setdb1 depletion in vivo is dependent mainly on natural killer (NK) cell-mediated cytotoxicity. Mechanistically, SETDB1 depletion upregulates interferon-stimulated genes and NKG2D ligands through the demethylation of histone H3 Lys9 at the enhancer regions, thereby enhancing their immunogenicity to NK cells and intrinsic apoptosis. Importantly, these effects are not observed in non-monocytic leukemia cells. We also identified the expression of myeloid cell nuclear differentiation antigen (MNDA) and its murine counterpart Ifi203 as biomarkers to predict the sensitivity of AML to SETDB1 depletion. Our study highlights the critical and selective role of SETDB1 in AML with granulo-monocytic differentiation and underscores its potential as a therapeutic target for current unmet needs.

The relationship of C-Reactive Protein to Albumin Ratio and interval debulking surgery outcome after neoadjuvant chemotherapy in ovarian cancer patients.

OBJECTIVE: To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients. METHODS: A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state. RESULTS: The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause. CONCLUSION: CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

[Preparation Method and Quality Evaluation of Novel Frozen Human Platelets].

OBJECTIVE: To optimize the technical parameters related to the preparation of novel frozen human platelets and formulate corresponding protocol for its preparation. METHODS: Novel frozen human platelets were prepared with O-type bagged platelet-rich plasma (PRP), the key technical parameters (DMSO addition, incubation time, centrifugation conditions, etc.) of the preparation process were optimized, and the quality of the frozen platelets was evaluated by routine blood tests, apoptosis rate, platelet activation rate and surface protein expression level. RESULTS: In the preparation protocol of novel frozen human platelets, the operation of centrifugation to remove supernatant was adjusted to before the procedure of platelets freezing, and the effect of centrifugation on platelets was minimal when the centrifugation condition was 800×g for 8 min. In addition, platelets incubated with DMSO for 30 min before centrifugation exhibited better quality after freezing and thawing. The indexes of novel frozen human platelets prepared with this protocol remained stable after long-term cryopreservation. CONCLUSION: The preparation technique of novel frozen human platelets was established and the protocol was formulated. It was also confirmed that the quality of frozen platelets could be improved by incubating platelets with DMSO for 30 min and then centrifuging them at 800×g for 8 min in the preparation of novel frozen human platelets.

Feasibility exploration of cortical auditory evoked potentials evoked by spectro-temporal modulation signals.

BACKGROUND: An objective measurement of speech perception would be valuable in hearing-impaired patients who are unable to perform auditory tasks reliably. OBJECTIVES: To investigate the feasibility of cortical auditory evoked potentials (CAEPs) evoked by different spectro-temporal modulation (STM) signals and provide reference for the further exploration of acoustic change complex (ACC) in hearing-impaired patients. METHOD: 29 normal hearing (NH) adults were recruited and stimulated randomly by STM signals at 6 spectral modulation rates: 0, 1, 2, 4, 8, 16 cycles/octave, at each of 4 temporal modulation rates: 0, 2, 4, 8 Hz, to elicit ACC response. RESULTS: The change of spectral modulation rates ≤ 16 cycles/octave at 0 Hz temporal modulation rate had different impacts on latency. 0, 1 cycles/octave, and 4, 8 Hz made a difference to the P2-N1 amplitude easily. 8, 16 cycles/octave were more unstable in rejection rate. No significant difference existed in waveform repetition rate among different STM rates. No significant interaction effect existed in spectral and temporal modulation. CONCLUSIONS: STM as a stimulus signal to induce ACC response had its feasibility. 2 cycles/octave at spectral modulation rate and 2 Hz at temporal modulation rate had better stability and waveform repeatability in NH adults.

A case report of acute Q fever with low-read detection of Coxiella burnetii genome by next-generation metagenomic sequencing.

The case presents a 47-year-old man with sudden abdominal pain and fever, but the cause was uncertain. Through metagenomic next-generation sequencing (mNGS) and detecting Q fever antibodies in serum, along with the patient's clinical and epidemiological history, a precise diagnosis was made, enabling timely and proper treatment.

Unraveling mechanisms of protein encapsulation and release in coacervates via molecular dynamics and machine learning.

Coacervates play a pivotal role in protein-based drug delivery research, yet their drug encapsulation and release mechanisms remain poorly understood. Here, we utilized the Martini model to investigate bovine serum albumin (BSA) protein encapsulation and release within polylysine/polyglutamate (PLys/PGlu) coacervates. Our findings emphasize the importance of ingredient addition sequence in coacervate formation and encapsulation rates, attributed to preference contact between oppositely charged proteins and poly(amino acid)s. Notably, coacervates composed of ß-sheet poly(amino acid)s demonstrate greater BSA encapsulation efficiency due to their reduced entropy and flexibility. Furthermore, we examined the pH responsiveness of coacervates, shedding light on the dissolution process driven by Coulomb forces. By leveraging machine learning algorithms to analyze simulation results, our research advances the understanding of coacervate-based drug delivery systems, with the ultimate goal of optimizing therapeutic outcomes.