Effect of Acupuncture Treatment on the Ocular Pain, Mental State and Ocular Surface Characteristics of Patients with Dry Eye Disease: A Non-Randomized Pilot Study.

Background: Ocular pain is a prevalent symptom of dry eye disease (DED), which often accompanies potential psychological issues. The study aimed to explore whether acupuncture could improve ocular pain, mental state, and dry eye parameters in patients with DED. Methods: The non-randomized pilot study included 48 patients divided into two groups: the acupuncture group (n=27) and the 0.3% sodium hyaluronate (SH) group (n=21). Participants in the acupuncture group underwent treatments on six bilateral acupuncture points (BL1, BL2, ST1, LI 20, SI1 and SI3) 3 times per week for 4 weeks. Patients in the SH group received 0.3% SH 4 times per day for 4 weeks. Ocular pain was assessed using the numerical rating scale (NRS), and mental state was evaluated through the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Ocular surface parameters, concentrations of inflammatory cytokines, and corneal nerve morphological indicators were measured at baseline, the first week, and the fourth week. Randomization procedures were not used in this study, and outcome assessors and statistical analysts were blinded. Results: Compared with baseline, both NRS scores (from 5.91 ± 1.52 to 1.94 ± 1.57) and ocular surface discomfort index (OSDI) scores (from 49.75 ± 14.92 to 29.64 ± 18.79) were decreased after 1 and 4 weeks of treatment in both groups (all p < 0.05). At 4 weeks, the acupuncture group showed significant improvements, including increased tear break-up time (TBUT) and corneal perception, decreased SAS and SDS scores, and reduced concentrations of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α concentration in tears (all p < 0.05). These changes were not observed in the SH group (all p > 0.05). Conclusion: Acupuncture treatment could improve ocular surface characteristics in patients with DED, and more importantly, it alleviates their ocular pain and depressive state. The anti-inflammatory effect of acupuncture may be involved in this process. Future research with larger, randomized controlled trials (RCTs) is necessary to confirm these findings and clarify the mechanisms involved.

CD103+ cDC1 Dendritic Cell Vaccine Therapy for Osteosarcoma Lung Metastases.

BACKGROUND: We generated a CD103+DC vaccine using K7M3 OS cell lysates (cDCV) and investigated its ability to induce regression of primary tumors, established lung metastases, and a systemic immune response. METHODS: A bilateral tumor model was used to assess cDCV therapy efficacy and systemic immunity induction. K7M3 cells were injected into mice bilaterally. Right-sided tumors received PBS (control) or cDCV. Left-sided tumors were untreated. Tumor growth was compared between the vaccine-treated and untreated tumor on the contralateral side and compared to the control group. The immune cell profiles of the tumors, and tumor-draining lymph nodes (TdLNs) and spleen were evaluated. To determine the efficacy of systemic cDCV therapy against established lung metastases, K7M3 cells were injected intratibially. Leg amputation was performed 5 weeks later. Mice were treated intravenously with PBS or cDCV and euthanized 6 weeks later. Lungs, TdLNs and spleen were collected. The number and size of the lung nodules were quantified. The immune cell profile of tumor, and lymph nodes and spleen were also evaluated. Using this same model, we evaluated the effect of cDCV + anti-CTLA-4. RESULTS: cDCV therapy inhibited the treated and untreated tumors and increased the number of T-cells in these tumors and the lymph nodes compared to control-treated mice. Systemic cDCV therapy administered following amputation decreased the size and number of lung metastases, and increased T-cell numbers in the tumor and lymph nodes. Combining anti-CTLA-4 with cDCV therapy increased cDCV efficacy against lung metastases. CONCLUSIONS: Intratumor cDCV generated a systemic immune response inhibiting the growth of both the treated and untreated tumors, with increased T-cells in the tumor and lymph nodes. Systemic cDCV was effective against established lung metastases. Efficacy was increased by anti-CTLA4. cDCVs may provide a novel therapeutic approach for relapsed/metastatic OS patients.

EPOC: A 28-nm 5.3 pJ/SOP Event-driven Parallel Neuromorphic Hardware with Neuromodulation-based Online Learning.

Bio-inspired neuromorphic hardware with learning ability is highly promising to achieve human-like intelligence, particularly in terms of high energy efficiency and strong environmental adaptability. Though many customized prototypes have demonstrated learning ability, learning on neuromorphic hardware still lacks a bio-plausible and unified learning framework, and inherent spike-based sparsity and parallelism have not been fully exploited, which fundamentally limits their computational efficiency and scale. Therefore, we develop a unified, event-driven, and massively parallel multi-core neuromorphic online learning processor, namely EPOC. We present a neuromodulation-based neuromorphic online learning framework to unify various learning algorithms, and EPOC supports high-accuracy local/global supervised Spike Neural Network (SNN) learning with a low-memory-demand streaming single-sample learning strategy through different neuromodulator formulations. EPOC leverages a novel event-driven computation method that fully exploits spike-based sparsity throughout the forward-backward learning phases, and parallel multi-channel and multi-core computing architecture, bringing 9.9× time efficiency improvement compared with the baseline architecture. We synthesize EPOC in a 28-nm CMOS process and perform extensive benchmarking. EPOC achieves state-of-the-art learning accuracy of 99.2%, 98.2%, and 94.3% on the MNIST, NMNIST, and DVS-Gesture benchmarks, respectively. Local-learning EPOC achieves 2.9× time efficiency improvement compared with the global learning counterpart. EPOC operates at a typical clock frequency of 100 MHz, providing a peak 328 GOPS/51 GSOPS throughput and a 5.3 pJ/SOP energy efficiency.

An explore method for quick screening biomarkers based on effective enrichment capacity and data mining.

Protein glycosylation acts as a crucial role in regulating protein function and maintaining cellular homeostasis. Efficient peptide enrichment can be utilized to effectively solve the inherent challenges of protein glycosylation analysis to search unknown cancer biomarkers. In this research, a low dimensional porous hydrophilic nanosheets with a multi-level porous structure (Co-MOF-SiO2@HA) was synthetized via an easy one-pot method for the efficient enrichment of the N-glycopeptides in the digests of complex biosamples. The synthetized nanosheets Co-MOF-SiO2@HA demonstrated excellent enriching performances including a high enrichment capacity (300 mg g-1 calculated), a spectacular selectivity (IgG digests and BSA digests at the molar ratio of 1/1200), and an excellent spatial confinement ability (IgG digests, IgG and BSA at the molar ratio of 1/1000/1000). As an explore result, after the enrichment of human colorectal cancer tissue and human healthy tissue by the nanosheets, several proteins related to cancers and one protein directly related to well-known human colorectal cancer were identified by detecting the corresponding glycopeptides. It presented the potential value of the feasibility of this analysis mode by nanosheets Co-MOF-SiO2@HA in proteomic analysis.

Rational Strategies for Preparing Highly Efficient Tin-, Bismuth- or Indium Based Electrocatalysts for Electrochemical CO2 Reduction to Formic acid.

Electrochemical carbon dioxide reduction reaction (CO2RR) is an environmentally friendly and economically viable approach to convert greenhouse gas CO2 into valuable chemical fuels and feedstocks. Among various products of CO2RR, formic acid/formate (HCOOH/HCOO-) is considered the most attractive one with its high energy density and ease of storage, thereby enabling widespread commercial applications in chemical, medicine, and energy-related industries. Nowadays, the development of efficient and financially feasible electrocatalysts with excellent selectivity and activity towards HCOOH/HCOO- is paramount for the industrial application of CO2RR technology, in which Tin (Sn), Bismuth (Bi), and Indium (In)-based electrocatalysts have drawn significant attention due to their high efficiency and various regulation strategies have been explored to design diverse advanced electrocatalysts. Herein, we comprehensively review the rational strategies to enhance electrocatalytic performances of these electrocatalysts for CO2RR to HCOOH/HCOO-. Specifically, the internal mechanism between the physicochemical properties of engineering materials and electrocatalytic performance is analyzed and discussed in details. Besides, the current challenges and future opportunities are proposed to provide inspiration for the development of more efficient electrocatalysts in this field.

Revisiting Virchow's triad: exploring the cellular and molecular alterations in cerebral venous congestion.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow's triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling. RESULTS: This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood. CONCLUSION: Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow's triad in the context of CVC.

GhCASPL1 regulates secondary cell wall thickening in cotton fibers by stabilizing the cellulose synthase complex on the plasma membrane.

Cotton (Gossypium hirsutum) fibers are elongated single cells that rapidly accumulate cellulose during secondary cell wall (SCW) thickening, which requires cellulose synthase complex (CSC) activity. Here, we describe the CSC-interacting factor CASPARIAN STRIP MEMBRANE DOMAIN-LIKE1 (GhCASPL1), which contributes to SCW thickening by influencing CSC stability on the plasma membrane. GhCASPL1 is preferentially expressed in fiber cells during SCW biosynthesis and encodes a MARVEL domain protein. The ghcaspl1 ghcaspl2 mutant exhibited reduced plant height and produced mature fibers with fewer natural twists, lower tensile strength, and a thinner SCW compared to the wild type. Similarly, the Arabidopsis (Arabidopsis thaliana) caspl1 caspl2 double mutant showed a lower cellulose content and thinner cell walls in the stem vasculature than the wild type but normal plant morphology. Introducing the cotton gene GhCASPL1 successfully restored the reduced cellulose content of the Arabidopsis caspl1 caspl2 mutant. Detergent treatments, ultracentrifugation assays, and enzymatic assays showed that the CSC in the ghcaspl1 ghcaspl2 double mutant showed reduced membrane binding and decreased enzyme activity compared to the wild type. GhCASPL1 binds strongly to phosphatidic acid (PA), which is present in much higher amounts in thickening fiber cells compared to ovules and leaves. Mutating the PA-binding site in GhCASPL1 resulted in the loss of its colocalization with GhCesA8, and it failed to localize to the plasma membrane. PA may alter membrane structure to facilitate protein-protein interactions, suggesting that GhCASPL1 and PA collaboratively stabilize the CSC. Our findings shed light on CASPL functions and the molecular machinery behind SCW biosynthesis in cotton fibers.

EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

Complex Phase Transitions of Fully Rigid Sphere-Rod Amphiphiles Induced by Solvent Polarity in Dilute Solutions.

We report complex macrophase and microphase transitions of rigid amphiphiles with spherical Keggin molecular clusters as the solvophilic block and rod-like rigid oligofluorene (OF) as the solvophobic block in mixed solvents of water and polar organic solvent. By properly adjusting the solvent polarity, the amphiphiles are found to respond accordingly by self-assembling into multilayered incomplete onion-like structures (10-25 vol % THF), single-layered vesicular structures (60 vol % THF), and an unexpected macrophase separation in the middle (40-50 vol % THF), which is due to the anomalous trends in Keggin solubility as a result of the nature of TBA+ counterions. The rigidity of the OF block prevents the amphiphile from assembling by following the rule of packing parameters; instead, interdigitation among different rods leads to the formation of the solvophobic domain to achieve self-assembly. The incomplete onion structures are controlled by the interdigitation of rigid rods for the number of layers and the electrostatic interaction among Keggin head groups for the interlayer distance. When the degree of interdigitation becomes lower, the self-assembly process shows a trend that can be explained by the traditional rule of packing parameter. This study demonstrates the formation of different self-assembled structures by rigid amphiphiles and their transitions induced by solvent composition. The self-assembly (microphase separation) of rigid amphiphiles in a dilute solution could indeed represent a broad area containing complicated, uncharted rules.

Universal droplet propulsion by dynamic surface-charge wetting.

Controllable droplet propulsion on solid surfaces plays a crucial role in various technologies. Many actuating methods have been developed; however, there are still some limitations in terms of the introduction of additives, the versatilities of solid surfaces, and the speed of transportation. Herein, we have demonstrated a universal droplet propulsion method based on dynamic surface-charge wetting by depositing oscillating and opposite surface charges on dielectric films with unmodified surfaces. Dynamic surface-charge wetting propels droplets by continuously inducing smaller front contact angles than rear contact angles. This innovative imbalance is built by alternately storing and spreading opposite charges on dielectric films, which results in remarkable electrostatic forces under large gradients and electric fields. The method exhibits excellent droplet manipulation performance characteristics, including high speed (~130 mm/s), high adaptability of droplet volume (1 µL-1 mL), strong handling ability on non-slippery surfaces with large contact angle hysteresis (CAH) (maximum angle of 35°), significant programmability and reconfigurability, and low mass loss. The great application potential of this method has been effectively demonstrated in programmable microreactions, defogging without gravity assistance, and surface cleaning of photovoltaic panels using condensed droplets.

The regulation of NFKB1 on CD200R1 expression and their potential roles in Parkinson's disease.

BACKGROUND: Overactivated microglia are a key contributor to Parkinson's disease (PD) by inducing neuroinflammation. CD200R1, a membrane glycoprotein mainly found on microglia, is crucial for maintaining quiescence with its dysregulation linked to microglia's abnormal activation. We and other groups have reported a decline in CD200R1 levels in several neurological disorders including PD. However, the mechanism regulating CD200R1 expression and the specific reasons for its reduction in PD remain largely unexplored. Given the pivotal role of transcription factors in gene expression, this study aimed to elucidate the transcriptional regulation of CD200R1 and its implications in PD. METHODS: The CD200R1 promoter core region was identified via luciferase assays. Potential transcription factors were predicted using the UCSC ChIP-seq database and JASPAR. NFKB1 binding to the CD200R1 core promoter was substantiated through electrophoretic mobility shift and chromatin immunoprecipitation assays. Knocking-down or overexpressing NFKB1 validated its regulatory effect on CD200R1. Correlation between decreased CD200R1 and deficient NFKB1 was studied using Genotype-Tissue Expression database. The clinical samples of the peripheral blood mononuclear cells were acquired from 44 PD patients (mean age 64.13 ± 9.78, 43.2% male, median Hoehn-Yahr stage 1.77) and 45 controls (mean age 64.70 ± 9.41, 52.1% male). NFKB1 knockout mice were utilized to study the impact of NFKB1 on CD200R1 expression and to assess their roles in PD pathophysiology. RESULTS: The study identified the CD200R1 core promoter region, located 482 to 146 bp upstream of its translation initiation site, was directly regulated by NFKB1. Significant correlation between NFKB1 and CD200R1 expression was observed in human PMBCs. Both NFKB1 and CD200R1 were significantly decreased in PD patient samples. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. CONCLUSION: Our study identified that NFKB1 served as a direct regulator of CD200R1. Reduced NFKB1 played a critical role in CD200R1 dysregulation and subsequent microglia overactivation in PD. These findings provide evidence that targeting the NFKB1-CD200R1 axis would be a novel therapeutic strategy for PD.

Calibration-free and ready-to-use wearable electroanalytical reporting system (r-WEAR) for long-term remote monitoring of electrolytes markers.

A major bottleneck in the development of wearable ion-selective sensors is the inherent conditioning and calibration procedures at the user's end due to the signal's instability and non-uniformity. To address this challenge, we developed a strategy that integrates three interdependent materials and device engineering approaches to realize a Ready-to-use Wearable ElectroAnalytical Reporting system (r-WEAR) for reliable electrolytes monitoring. The strategy collectively utilized (1) finely-configured diffusion-limiting polymers to stabilize the electromotive force in the electrodes, (2) a uniform electrical induction in electrochemical cells to normalize the open-circuit potential (OCP), and (3) an electrical shunt to maintain the OCP across the entire sensor in the r-WEAR. The approaches jointly enable fabrication of homogeneously stable and uniform ion-selective sensors, eliminating common conditioning and calibration practices. As a result, the r-WEAR demonstrated a signal's variation down to ±1.99 mV with a signal drift of 0.5 % per hour (0.12 mV h-1) during a 12-h continuous measurement of 10 sensors and a signal drift as low as 13.3 µV h-1 during storage. On-body evaluations of the r-WEAR for four days without conditioning and re-/calibration further validated the sensor's performance in realistic settings, indicating its remarkable potential for practical usage in a user operation-free manner in wearable healthcare applications.

A Two-Step Intermolecular Interaction Of Molecular Macroions With Multivalent Counterions.

Macroion-counterion interaction is essential for regulating the solution behaviors of hydrophilic macroions, as simple models for polyelectrolytes. Here, we explore the interaction between uranyl peroxide molecular cluster Li68K12(OH)20[UO2(O2)OH]60 (U60) and multivalent counterions. Different from interaction with monovalent counterions that shows a simple one-step process, isothermal titration calorimetry, combined with light/X-ray scattering measurements and electron microscopy, confirm a two-step process for their interaction with multivalent counterions: an ion-pairing between U60 and the counterion with partial breakage of hydration shells followed by strong U60-U60 attraction, leading to the formation of large nanosheets with severe breakage and reconstruction of hydration shells. The detailed studies on macroion-counterion interaction can be nicely correlated to the microscopic (self-assembly) and macroscopic (gelation or phase separation) phase transitions in the dilute U60 aqueous solutions induced by multivalent counterions.

The pentatricopeptide repeat protein DG1 promotes the transition to bilateral symmetry during Arabidopsis embryogenesis through GUN1-mediated plastid signals.

During Arabidopsis embryogenesis, the transition of the embryo's symmetry from radial to bilateral between the globular and heart stage is a crucial event, involving the formation of cotyledon primordia and concurrently the establishment of a shoot apical meristem (SAM). However, a coherent framework of how this transition is achieved remains to be elucidated. In this study, we investigated the function of DELAYED GREENING 1 (DG1) in Arabidopsis embryogenesis using a newly identified dg1-3 mutant. The absence of chloroplast-localized DG1 in the mutants led to embryos being arrested at the globular or heart stage, accompanied by an expansion of WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM) expression. This finding pinpoints the essential role of DG1 in regulating the transition to bilateral symmetry. Furthermore, we showed that this regulation of DG1 may not depend on its role in plastid RNA editing. Nevertheless, we demonstrated that the DG1 function in establishing bilateral symmetry is genetically mediated by GENOMES UNCOUPLED 1 (GUN1), which represses the transition process in dg1-3 embryos. Collectively, our results reveal that DG1 functionally antagonizes GUN1 to promote the transition of the Arabidopsis embryo's symmetry from radial to bilateral and highlight the role of plastid signals in regulating pattern formation during plant embryogenesis.

Is fluorometric sentinel lymph node biopsy in endometrial cancer necessary?

Objective: In this study, we collected perioperative and postoperative follow-up data from patients with endometrial cancer (EC) at different stages to evaluate the role of sentinel lymph node biopsy (SLNB) in endometrial cancer surgery. Methods: A total of 186 endometrial cancer patients undergoing radical hysterectomy from January 2018 to April 2022 were retrospectively analyzed. Patients were classified into four groups. Group A comprised patients diagnosed with stage IA grade 1 and 2 endometrioid EC who underwent SLNB. Group B comprised patients with stage IA grade 1 and 2 endometrioid EC who did not undergo SLNB. Group C comprised patients with higher-grade endometrioid EC, wherein systematic lymph node dissection was performed based on SLNB results. Group D comprised patients with higher-grade endometrioid EC who did not undergo SLNB and instead underwent direct systematic lymph node dissection. Clinical, pathological data, and follow-up information for all patients were collected. Results: In Group A and B, SLNB was performed on 36 out of 67 patients with IA stage 1 and 2 endometrial cancer, yielding a SLN positivity rate of 5.6%. There were no significant differences observed between the two groups regarding perioperative outcomes and postoperative follow-up. Conversely, among 119 patients with higher-grade endometrial cancer, 52 underwent SLNB, with 20 patients exhibiting SLN positivity, resulting in a SLN positivity rate of 38.4%. However, the decision to undergo SLNB did not yield significant differences in perioperative outcomes and postoperative follow-up among these patients. Conclusion: For stage IA grade 1 and 2 endometrioid EC, the incidence of lymph node positivity is low, omitting SLNB in this subpopulation is a feasible option. In other stages of endometrioid EC, there is no significant difference in perioperative and postoperative follow-up data between patients undergoing routine systematic lymphadenectomy and those undergoing systematic lymphadenectomy based on SLNB results. Therefore, if SLNB is not available, the standard procedure of PLND remains an option to obtain information about lymph node status, despite the surgical complications associated with this procedure.

Clinical Characteristic and Tear Film Biomarkers After Myopic FS-LASIK: 1-Year Prospective Follow-up.

PURPOSE: To assess the long-term (1-year) effect of myopic femtosecond laser-assisted in situ keratomileusis (FSLASIK) on clinical characteristics and tear film biomarkers. METHODS: Eighty eyes from 80 patients who underwent FSLASIK were evaluated. Ocular surface symptoms and signs were evaluated using specific questionnaires and tests. The corneal nerves and dendritic cells were examined using in vivo confocal microscopy. Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. Tear inflammatory cytokines and neuropeptides were evaluated using Luminex immunoassay. These examinations were performed preoperatively and at 1, 3, 6, and 12 months postoperatively. RESULTS: Seventy-three participants completed all follow-up visits. Following FS-LASIK, ocular symptoms and signs (except Schirmer I test) worsened at 1 month but corneal and conjunctival stainings improved by 3 months. The numbers of dendritic cells and activated dendritic cells increased at the 3-month postoperative visit and recovered to preoperative levels by the 6-month visit. Ocular symptoms and corneal sensitivity recovered to preoperative levels at the 12-month visit. Tear break-up time and corneal nerve morphology were not recovered to preoperative status at the 12-month visit. Interleukin (IL)-1ß, IL-17A, tumor necrosis factor-α, and substance P tear levels significantly increased at all postoperative visits compared to preoperative levels. Corneal staining scores positively correlated with tear IL-1ß and IL-17A levels, whereas corneal nerve morphology positively correlated with corneal sensitivity and negatively correlated with substance P levels. CONCLUSIONS: Although most clinical variables improved at 12 months postoperatively, some tear inflammatory cytokines and substance P remain altered beyond 12 months, indicating that ocular homeostasis is not completely recovered. [J Refract Surg. 2024;40(8):e508-e519.].

KHSRP Stabilizes m6A-Modified Transcripts to Activate FAK Signaling and Promote Pancreatic Ductal Adenocarcinoma Progression.

N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

The architecture of functional brain network modulated by driving under train running noise exposure.

A noisy environment can considerably impact drivers' attention and fatigue, endangering driving safety. Consequently, this study designed a simulated driving experimental scenario to analyse the effects of noise generated during urban rail transit train operation on drivers' functional brain networks. The experiment recruited 16 participants, and the simulated driving scenario was conducted at noise levels of 50, 60, 70, and 80 dB. Functional connectivity between all electrode pairs across various frequency bands was evaluated using the weighted phase lag index (WPLI), and a brain network based on this was constructed. Graph theoretic analysis employed network global efficiency, degree, and clustering coefficient as metrics. Significant increases in the WPLI values of theta and alpha frequency bands were observed in high noise environments (70 dB, 80 dB), as well as enhanced brain synchronisation. Furthermore, concerning the topological metrics of brain networks, it was observed that the global efficiency of brain networks in theta and alpha frequency ranges, as well as the node degree and clustering coefficients, experienced substantial growth in high noise environments (70 dB, 80 dB) as opposed to 50 dB and 60 dB. This finding indicates that high-noise environments impact the reorganisation of functional brain networks, leading to a preference for network structures with improved global efficiency. Such findings may improve our understanding of the neural mechanisms of driving under noise exposure, and thus potentially reduce road accidents to some extent.

Lnc NBAT1 Inhibits the Proliferation and Migration of Liver Cancer Cells Through the miR-21/PDCD4/AP-1 Signaling Axis.

Long non-coding RNAs (Lnc RNAs) are proven to participate in liver cancer (LC) regulation. The regulation of miR-21 by lnc NBAT1 has been studied in other cancers. However, the effect of this regulation on LC and its specific mechanism remains unclear. Lnc NBAT1 and miR-21 expressions in clinical tissues were measured by RT-qPCR. PDCD4, AP-1, p-c-Fos, p-c-Jun, and cyclin D1 expressions were analyzed by Western blot. Overexpression of lnc NBAT1 was studied to explore its influence on malignant behaviors of Bel7402 cells and the development of LC in the xenograft mouse model (XMM). The regulation mechanism of lnc NBAT1 in LC was explored by lnc NBAT1 overexpression, miR-21 mimic treatment, or PDCD4 silencing in Bel7402 cells. Lnc NBAT1 expression was downregulated while miR-21 expression was upregulated in LC tissues and cell lines. In comparison with LX-2 cells, the expressions of PDCD4 and AP-1 were downregulated in Bel7402 cells, while those of p-c-Fos, p-c-Jun, and cyclin D1 were upregulated. Further, lnc NBAT1 was found to localize primarily in the cytoplasm of Bel7402 cells. Overexpression of lnc NBAT1 enhanced cell apoptosis, blocked the cell cycle, suppressed malignant behaviors of Bel7402 cells, and inhibited tumor progression in the XMM. Mechanistically, lnc NBAT1 functioned as a competing endogenous RNA (ceRNA) by binding to the downstream target miR-21 to stabilize the expressions of PDCD4 and AP-1, thereby inhibiting malignant behaviors of Bel7402 cells. Lnc NBAT1 suppressed malignant behaviors of LC cells through the miR-21/PDCD4/AP-1 axis. Lnc NBAT1 might be a promising biomarker for LC treatment.

Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review.

Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), the interactions at the organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply for intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks in both healthy and pathological conditions. In this review, we summarized mitochondrial transfer events, relevant routes, and underlying molecular mechanisms originating from diverse cell populations within NVU. We particularly focus on the therapeutic potential of this mechanism in treating central nervous system disorders, notably neurodegenerative diseases marked by mitochondrial dysfunction and then highlight the promising prospects of exogenous mitochondrial supplementation as a treatment target.