Relationship between syncopal symptoms and head-up tilt test modes.

OBJECTIVE: Head-up tilt test (HUTT) is an important tool in the diagnosis of pediatric vasovagal syncope. This research will explore the relationship between syncopal symptoms and HUTT modes in pediatric vasovagal syncope. METHODS: A retrospective analysis was performed on the clinical data of 2513 children aged 3-18 years, who were diagnosed with vasovagal syncope, from Jan. 2001 to Dec. 2021 due to unexplained syncope or pre-syncope. The average age was 11.76 ± 2.83 years, including 1124 males and 1389 females. The patients were divided into the basic head-up tilt test (BHUT) group (596 patients) and the sublingual nitroglycerine head-up tilt test (SNHUT) group (1917 patients) according to the mode of positive HUTT at the time of confirmed pediatric vasovagal syncope. RESULTS: (1) Baseline characteristics: Age, height, weight, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and composition ratio of syncope at baseline status were higher in the BHUT group than in the SNHUT group (all P < 0.05). (2) Univariate analysis: Age, height, weight, HR, SBP, DBP, and syncope were potential risk factors for BHUT positive (all P < 0.05). (3) Multivariate analysis: syncope was an independent risk factor for BHUT positive, with a probability increase of 121% compared to pre-syncope (P<0.001). CONCLUSION: The probability of BHUT positivity was significantly higher than SNHUT in pediatric vasovagal syncope with previous syncopal episodes.

Preparation of PLCL/ECM nerve conduits by electrostatic spinning technique and evaluationin vitroandin vivo.

Objective. Artificial nerve scaffolds composed of polymers have attracted great attention as an alternative for autologous nerve grafts recently. Due to their poor bioactivity, satisfactory nerve repair could not be achieved. To solve this problem, we introduced extracellular matrix (ECM) to optimize the materials.Approach.In this study, the ECM extracted from porcine nerves was mixed with Poly(L-Lactide-co-ϵ-caprolactone) (PLCL), and the innovative PLCL/ECM nerve repair conduits were prepared by electrostatic spinning technology. The novel conduits were characterized by scanning electron microscopy (SEM), tensile properties, and suture retention strength test for micromorphology and mechanical strength. The biosafety and biocompatibility of PLCL/ECM nerve conduits were evaluated by cytotoxicity assay with Mouse fibroblast cells and cell adhesion assay with RSC 96 cells, and the effects of PLCL/ECM nerve conduits on the gene expression in Schwann cells was analyzed by real-time polymerase chain reaction (RT-PCR). Moreover, a 10 mm rat (Male Wistar rat) sciatic defect was bridged with a PLCL/ECM nerve conduit, and nerve regeneration was evaluated by walking track, mid-shank circumference, electrophysiology, and histomorphology analyses.Main results.The results showed that PLCL/ECM conduits have similar microstructure and mechanical strength compared with PLCL conduits. The cytotoxicity assay demonstrates better biosafety and biocompatibility of PLCL/ECM nerve conduits. And the cell adhesion assay further verifies that the addition of ECM is more beneficial to cell adhesion and proliferation. RT-PCR showed that the PLCL/ECM nerve conduit was more favorable to the gene expression of functional proteins of Schwann cells. Thein vivoresults indicated that PLCL/ECM nerve conduits possess excellent biocompatibility and exhibit a superior capacity to promote peripheral nerve repair.Significance.The addition of ECM significantly improved the biocompatibility and bioactivity of PLCL, while the PLCL/ECM nerve conduit gained the appropriate mechanical strength from PLCL, which has great potential for clinical repair of peripheral nerve injuries.

Consolidated guidance for behavioral intervention pilot and feasibility studies.

BACKGROUND: In the behavioral sciences, conducting pilot and/or feasibility studies (PFS) is a key step that provides essential information used to inform the design, conduct, and implementation of a larger-scale trial. There are more than 160 published guidelines, reporting checklists, frameworks, and recommendations related to PFS. All of these publications offer some form of guidance on PFS, but many focus on one or a few topics. This makes it difficult for researchers wanting to gain a broader understanding of all the relevant and important aspects of PFS and requires them to seek out multiple sources of information, which increases the risk of missing key considerations to incorporate into their PFS. The purpose of this study was to develop a consolidated set of considerations for the design, conduct, implementation, and reporting of PFS for interventions conducted in the behavioral sciences. METHODS: To develop this consolidation, we undertook a review of the published guidance on PFS in combination with expert consensus (via a Delphi study) from the authors who wrote such guidance to inform the identified considerations. A total of 161 PFS-related guidelines, checklists, frameworks, and recommendations were identified via a review of recently published behavioral intervention PFS and backward/forward citation tracking of a well-known PFS literature (e.g., CONSORT Ext. for PFS). Authors of all 161 PFS publications were invited to complete a three-round Delphi survey, which was used to guide the creation of a consolidated list of considerations to guide the design, conduct, and reporting of PFS conducted by researchers in the behavioral sciences. RESULTS: A total of 496 authors were invited to take part in the three-round Delphi survey (round 1, N = 46; round 2, N = 24; round 3, N = 22). A set of twenty considerations, broadly categorized into six themes (intervention design, study design, conduct of trial, implementation of intervention, statistical analysis, and reporting) were generated from a review of the 161 PFS-related publications as well as a synthesis of feedback from the three-round Delphi process. These 20 considerations are presented alongside a supporting narrative for each consideration as well as a crosswalk of all 161 publications aligned with each consideration for further reading. CONCLUSION: We leveraged expert opinion from researchers who have published PFS-related guidelines, checklists, frameworks, and recommendations on a wide range of topics and distilled this knowledge into a valuable and universal resource for researchers conducting PFS. Researchers may use these considerations alongside the previously published literature to guide decisions about all aspects of PFS, with the hope of creating and disseminating interventions with broad public health impact.

Dynamic encoding of temperature in the central circadian circuit coordinates physiological activities.

The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a's diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Low-Cost Recruitment Approach: Utilizing Facebook Groups to Recruit COVID-19 Long-Haulers.

Introduction: The accessibility of social media (e.g., Facebook groups) presents long-haulers with the ability to connect with others with similar experiences and symptomology that are likely outside of their physical social networks. Social media sites may serve as promising platforms for research recruitment, public health campaigns, or interventions. The present study aims to assess, and comprehensively present, the effectiveness of a low-cost approach to recruitment through groups on Facebook within the context of a broader study of COVID-19 long-haulers. Methods: Facebook groups were searched using a variety of COVID-related terminology and included if they were in English, COVID-19 specific, public, and have or were approaching 1,000 or more members. Group administrators were either contacted for permission to post recruitment materials or posts were made and left pending administrator approval, depending on group settings. Group members were able to follow a link to the online survey platform (i.e., RedCap) where they provided informed consent and completed an online assessment of their COVID-19 experiences and psychosocial wellbeing. Upon survey completion participants were able to opt-in to a raffle-based incentive. The characteristics of the Facebook groups and demographic background of participants were assessed. Findings: Contacting administrators and posts made between January and March of 2022 within 17 COVID-19 specific groups yielded a sample size of 460 long-haulers. The groups relied upon for recruitment had a mean size of 21,022 (SD=45,645.3), most had three or more administrators (43%), and a majority were state specific (60%). The long-hauler participants enrolled from the posts had an average age of 32 years (SD=6.19), approximately split between men (48.91%) and women (50.22%), a majority white (70%), having earned a bachelor's or postgraduate degree (63.48%), and reporting an annual income between $50,000 and $100,000 (56.09%). Discussion: The present study presents strengths and recommendations for survey recruitment through Facebook groups as a low-cost recruitment strategy that is easily targeted to populations with a specific health condition and allows users to complete online psycho-behavioral assessments off-site on a HIPPA compliant survey platform.

C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability.

Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFCGlu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFCGlu neurons in LPS-treated WT mice, C3aR-null mPFCGlu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFCGlu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFCGlu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.

Teachers' Perceptions of the Impact of the COVID-19 Pandemic and Their Implementation of an Evidence-based HIV Prevention Program in the Bahamas.

Information on how school-based programs is implemented and sustained during crises is limited. In this study, we assessed the impact of the COVID-19 pandemic on the implementation of a HIV prevention intervention in The Bahamas. Data were collected from 139 Grade 6 teachers in 2021-2022. Teachers attended virtual training and received implementation monitoring from coordinators. On average, teachers taught 26.4 (SD = 9.2) of the 35 core activities, and 7.4 (SD = 2.4) out of 9 sessions. More than half (58.3%) of teachers completed 28 or more core activities; 69.1% covered eight or all nine sessions, which is equivalent to 80% of the HIV intervention curriculum. Almost half of the teachers (43%) reported that the pandemic negatively impacted their ability to teach the program; 72% of teachers maintained that the program remained "very important" during times of crisis. Greater self-efficacy and supports increased implementation fidelity.

Effect of in vivo culture conditions on the proliferation and differentiation of rat adipose-derived stromal cells.

Adipose-derived stromal cells (ADSCs) are a promising stem cell sources for tissue engineering and cell-based therapy. However, long-term in vitro expansion of ADSCs impedes stemness maintenance, which is partly attributed to deprivation of their original microenvironment. Incompetent cells limit the therapeutic effects of ADSC-based clinical strategies. Therefore, reconstructing a more physiologically and physically relevant niche is an ideal strategy to address this issue and therefore facilitates the extensive application of ADSCs. Here, we transplanted separated ADSCs into local subcutaneous adipose tissues of nude mice as an in vivo cell culture model. We found that transplanted ADSCs maintained their primitive morphology and showed improved proliferation and delayed senescence compared to those of cells cultured in a incubator. Significantly increased expression of stemness-related markers and multilineage differentiation abilities were further observed in in vivo cultured ADSCs. Finally, sequencing revealed that genes whose expression differed between ADSCs obtained under in vivo and in vitro conditions were mainly located in the extracellular matrix and extracellular space and that these genes participate in regulating transcription and protein synthesis. Moreover, we found that an Egr1 signaling pathway might exert a crucial impact on controlling stemness properties. Our findings might collectively pave the way for ADSC-based applications.

Identification of metabolism-related key genes as potential biomarkers for pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.

Discovery of (±)-Penindolenes Reveals an Unusual Indole Ring Cleavage Pathway Catalyzed by P450 Monooxygenase.

(±)-Penindolenes A-D (1-4), the first representatives of indole terpenoids featuring a γ-lactam skeleton, were isolated from the mangrove-derived endophytic fungus Penicillium brocae MA-231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ-lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae  catalyzed the 2,3-cleavage of the indole ring to generate two keto groups in 1, in different manners from well-known tryptophan dioxygenases. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase-like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids.

Hydrogen sulfide mitigates memory impairments via the restoration of glutamatergic neurons in a mouse model of hemorrhage shock and resuscitation.

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased ß power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored ß power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased ß power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR.

Regulation of Dihydroartemisinin on the pathological progression of laryngeal carcinoma through the periostin/YAP/IL-6 pathway.

Objective: Laryngeal cancer (LC) is one of the most common squamous cell carcinomas of the head and neck in clinical practice, and its incidence has been increasing in recent years, but the prognosis of the patients is not favorable. Hence, it is critical to re-understand and deeply study the causes and mechanisms of LC and explore new effective treatment methods and strategies. In this study, we analyzed the effect of Dihydroartemisinin (DHA) on the pathological progression of LC through the periostin (POSTN)/Yes-associated protein (YAP)/interleukin (IL)-6 pathway, which can provide new clinical references and guidelines. Methods: POSTN, YAP, and IL-6 levels in 18 pairs of fresh LC tissues and adjacent counterparts in our hospital were detected. Additionally, LC TU686 cell line was purchased for DHA treatment of various concentrations to detect changes in cell biological behavior. Finally, we built a tumor-bearing mouse model with C57BL/6 mice and intragastrically administrated DHA to the animals to observe the growth of living tumors and to measure POSTN, YAP, and IL-6 expression in tumor tissues. Results: As indicated by PCR, Western blotting, and immunohistochemistry, POSTN, YAP, and IL-6 presented higher expression in LC tissues than in adjacent counterparts. In cell experiments, the cloning rate of LC cells decreased and the apoptosis rate increased after DHA intervention, with 160 µmol/L DHA contributing to the most significant effect on LC activity inhibition. Furthermore, DHA-intervened cells exhibited markedly reduced POSTN, YAP, and IL-6 levels. Finally, the tumorigenesis experiment in nude mice showed inhibited tumor growth after DHA administration. And consistently, the expressions of POSTN, YAP, and IL-6 in living tumors decreased. Conclusions: DHA can inhibit POSTN/YAP/IL-6 transduction, accelerate LC cell apoptosis, and alleviate the malignant progression of LC.

Association between serum apolipoprotein E and cognitive function in Chinese patients with temporal lobe epilepsy.

OBJECTIVE: To investigate the effect of serum apolipoprotein E (APOE) levels on cognitive function in patients with temporal lobe epilepsy (TLE). METHODS: Clinical data were collected from 190 subjects including 110 TLE patients and 80 healthy people. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. Serum levels of APOE were measured using ELISA kits. Genotyping of APOE in peripheral blood was detected by microarray hybridization. RESULTS: Patients with TLE had significantly lower ACE-R total score, memory and verbal fluency scores compared to the healthy group. Serum levels of APOE were significantly higher in TLE patients than in the healthy subjects. Serum APOE levels were significantly negatively correlated with ACE-R total score, memory and verbal fluency scores. The cognitive function score of TLE with APOE ε4 allele was lower than that of TLE without APOE ε4 allele. SIGNIFICANCE: Our study showed that serum APOE levels were higher in TLE patients than in the healthy population. And serum APOE levels were associated with cognitive dysfunction in TLE patients. APOE ε4 allele carriers have poor cognitive function in TLE patients.

Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

Long non-coding RNA DANCR increases spinal cord neuron apoptosis and inflammation of spinal cord injury by mediating the microRNA-146a-5p/MAPK6 axis.

OBJECTIVE: This research was to unravel the impact of the lncRNA differentiation antagonizing non-protein coding RNA (DANCR)/microRNA (miR)-146a-5p/mitogen-activated protein kinase 6 (MAPK6) axis on spinal cord injury (SCI). METHODS: SCI mouse models were established and injected with si-DANCR or miR-146a-5p agomir. The recovery of motor function was assessed by Basso Mouse Scale. SCI was pathologically evaluated, and serum inflammatory factors were measured in SCI mice. Mouse spinal cord neurons were injured by H2O2 and transfected, followed by assessment of proliferation and apoptosis. DANCR, miR-146a-5p, and MAPK6 in tissues and cells were detected, as well as their relationship. RESULTS: DANCR increased and miR-146a-5p decreased in SCI. Silencing DANCR or enhancing miR-146a-5p stimulated the proliferation of mouse spinal cord neurons and reduced apoptosis. DANCR was bound to miR-146a-5p to target MAPK6. DANCR affected the proliferation and apoptosis of spinal cord neurons by mediating the miR-146a-5p/MAPK6 axis. Downregulating DANCR or upregulating miR-146a-5p improved inflammation, the destruction of spinal cord tissue structure, and apoptosis in SCI mice. CONCLUSION: DANCR affects spinal cord neuron apoptosis and inflammation of SCI by mediating the miR-146a-5p/MAPK6 axis.

Interaction of Negative Bias Instability and Self-Heating Effect on Threshold Voltage and SRAM (Static Random-Access Memory) Stability of Nanosheet Field-Effect Transistors.

In this paper, we investigate the effects of negative bias instability (NBTI) and self-heating effect (SHE) on threshold voltage in NSFETs. To explore accurately the interaction between SHE and NBTI, we established an NBTI simulation framework based on trap microdynamics and considered the influence of the self-heating effect. The results show that NBTI weakens the SHE effect, while SHE exacerbates the NBTI effect. Since the width of the nanosheet in NSFET has a significant control effect on the electric field distribution, we also studied the effect of the width of the nanosheet on the NBTI and self-heating effect. The results show that increasing the width of the nanosheet will reduce the NBTI effect but will enhance the SHE effect. In addition, we extended our research to the SRAM cell circuit, and the results show that the NBTI effect will reduce the static noise margin (SNM) of the SRAM cell, and the NBTI effect affected by self-heating will make the SNM decrease more significantly. In addition, our research results also indicate that increasing the nanosheet width can help slow down the NBTI effect and the negative impact of NBTI on SRAM performance affected by the self-heating effect.

Minocycline-loaded nHAP/PLGA microspheres for prevention of injury-related corneal angiogenesis.

BACKGROUND: Corneal neovascularization (CoNV) threatens vision by disrupting corneal avascularity, however, current treatments, including pharmacotherapy and surgery, are hindered by limitations in efficacy and adverse effects. Minocycline, known for its anti-inflammatory properties, could suppress CoNV but faces challenges in effective delivery due to the cornea's unique structure. Therefore, in this study a novel drug delivery system using minocycline-loaded nano-hydroxyapatite/poly (lactic-co-glycolic acid) (nHAP/PLGA) nanoparticles was developed to improve treatment outcomes for CoNV. RESULTS: Ultra-small nHAP was synthesized using high gravity technology, then encapsulated in PLGA by a double emulsion method to form nHAP/PLGA microspheres, attenuating the acidic by-products of PLGA degradation. The MINO@PLGA nanocomplex, featuring sustained release and permeation properties, demonstrated an efficient delivery system for minocycline that significantly inhibited the CoNV area in an alkali-burn model without exhibiting apparent cytotoxicity. On day 14, the in vivo microscope examination and ex vivo CD31 staining corroborated the inhibition of neovascularization, with the significantly smaller CoNV area (29.40% ± 6.55%) in the MINO@PLGA Tid group (three times daily) than that of the control group (86.81% ± 15.71%), the MINO group (72.42% ± 30.15%), and the PLGA group (86.87% ± 14.94%) (p < 0.05). Fluorescein sodium staining show MINO@PLGA treatments, administered once daily (Qd) and three times daily (Tid) demonstrated rapid corneal epithelial healing while the Alkali injury group and the DEX group showed longer healing times (p < 0.05). Additionally, compared to the control group, treatments with dexamethasone, MINO, and MINO@PLGA were associated with an increased expression of TGF-ß as evidenced by immunofluorescence, while the levels of pro-inflammatory cytokines IL-1ß and TNF-α demonstrated a significant decrease following alkali burn. Safety evaluations, including assessments of renal and hepatic biomarkers, along with H&E staining of major organs, revealed no significant cytotoxicity of the MINO@PLGA nanocomplex in vivo. CONCLUSIONS: The novel MINO@PLGA nanocomplex, comprising minocycline-loaded nHAP/PLGA microspheres, has shown a substantial capacity for preventing CoNV. This study confirms the complex's ability to downregulate inflammatory pathways, significantly reducing CoNV with minimal cytotoxicity and high biosafety in vivo. Given these findings, MINO@PLGA stands as a highly promising candidate for ocular conditions characterized by CoNV.

New Hydroxyphenylacetic Acids and α-Pyrone Derivative from the Deep-Sea Cold Seep Sediment-Derived Fungus Penicillium corylophilum CS-682.

Two pairs of new enantiomeric hydroxyphenylacetic acid derivatives, (±)-corylophenols A and B ((±)-1 and (±)-2), a new α-pyrone analogue, corylopyrone A (3), and six andrastin-type meroterpenoids (4-9) were isolated and identified from the deep-sea cold-seep sediment-derived fungus Penicillium corylophilum CS-682. Their structures and stereo configurations were determined by detailed spectroscopic analysis of NMR and MS data, chiral HPLC analysis, J-based configuration analysis, and quantum chemical calculations of ECD, specific rotation, and NMR (with DP4+ probability analysis). Compound 3 showed inhibitory activity against some strains of pathogenic bacteria.

Electrochemical reductive removal of trichloroacetic acids by a three-dimensional binderless carbon nanotubes/ CoP/Co foam electrode: Performance and mechanism.

Numerous chlorinated disinfection by-products (DBPs) are produced during the chlorination disinfection of water. Among them, chloroacetic acids (CAAs) are of great concern due to their potential human carcinogenicity. In this study, effective electrocatalytic dechlorination of trichloroacetic acids (TCAA), a typical CAAs, was achieved in the electrochemical system with the three-dimensional (3D) self-supported CoP on cobalt foam modified by carbon nanotubes (CNT/CoP/CF) as the cathode. At a 10 mA cm-2 current density, 74.5% of TCAA (500 µg L-1) was converted into AA within 100 min. In-situ growth of CoP increased the effective electrochemical surface area of the electrode. Electrodeposited CNT promoted electron transfer from the electrode surface to TCAA. Therefore, the production of surface-adsorbed atomic hydrogen (H*) on CNT/CoP/CF was improved, further resulting in excellent electrochemical dechlorination of TCAA. The dechlorination pathway of TCAA proceeded into acetic acids via direct electronic transfer and H*-mediated reduction on CNT/CoP/CF electrode. Additionally, the electroreduction efficiency of CNT/CoP/CF for TCAA exceeded 81.22% even after 20 cycles. The highly efficient TCAA reduction performance (96.57%) in actual water revealed the potential applicability of CNT/CoP/CF in the complex water matrix. This study demonstrated that the CNT/CoP/CF is a promising non-noble metal cathode to remove chlorinated DBPs in practice.