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1.
BMC Geriatr ; 24(1): 492, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840066

ABSTRACT

BACKGROUND: There is limited understanding regarding prospective associations of insomnia symptoms and trajectories with functional disability. We aimed to investigate the associations of insomnia symptoms and trajectories with functional disability. METHOD: A total of 13 197 participants were eligible from the Health and Retirement Study. Insomnia symptoms included non-restorative sleep, difficulty initiating sleep, early morning awakening, and difficulty maintaining sleep. We also identified four distinct trajectories of insomnia symptoms: low, decreasing, increasing, and high insomnia symptoms. Functional status was assessed through activities of daily living (ADL) and instrumental activities of daily living (IADL). RESULTS: Participants experiencing one (HR, 1.21; 95% CI, 1.13-1.29), two (HR, 1.43; 95% CI, 1.29-1.57), or three to four (HR, 1.41; 95% CI, 1.25-1.60) insomnia symptoms had a higher risk of ADL disability than asymptomatic respondents. Similarly, participants with one or more insomnia symptoms had a higher risk of IADL disability. Furthermore, using the trajectory with low insomnia symptoms as the reference, decreasing insomnia symptoms (HR, 1.22; 95% CI, 1.12-1.34), increasing insomnia symptoms (HR, 1.21; 95% CI, 1.05-1.41), and high insomnia symptoms (HR, 1.36; 95% CI, 1.18-1.56) were all associated with an increased risk of ADL disability. CONCLUSION: Both a single measurement and dynamic trajectory of insomnia symptoms are associated with the onset of ADL disability. Increased awareness and management of insomnia symptoms may contribute to the prevention of functional disability occurrence.


Subject(s)
Activities of Daily Living , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/diagnosis , Female , Male , Prospective Studies , Aged , Middle Aged , Disabled Persons , Cohort Studies , Disability Evaluation , Risk Factors
2.
Thromb J ; 22(1): 47, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840142

ABSTRACT

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

3.
Fa Yi Xue Za Zhi ; 40(2): 186-191, 2024 Apr 25.
Article in English, Chinese | MEDLINE | ID: mdl-38847035

ABSTRACT

OBJECTIVES: To explore the postmortem diffusion rule of Aconitum alkaloids and their metabolites in poisoned rabbits, and to provide a reference for identifying the antemortem poisoning or postmortem poisoning of Aconitum alkaloids. METHODS: Twenty-four rabbits were sacrificed by tracheal clamps. After 1 hour, the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration. Then, they were placed supine and stored at 25 ℃. The biological samples from 3 randomly selected rabbits were collected including heart blood, peripheral blood, urine, heart, liver, spleen, lung and kidney tissues at 0 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h and 96 h after intragastric administration, respectively. Aconitum alkaloids and their metabolites in the biological samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: At 4 h after intragastric administration, Aconitum alkaloids and their metabolites could be detected in heart blood, peripheral blood and major organs, and the contents of them changed dynamically with the preservation time. The contents of Aconitum alkaloids and their metabolites were higher in the spleen, liver and lung, especially in the spleen which was closer to the stomach. The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration. In contrast, the contents of Aconitum alkaloids and their metabolites in kidney were all lower. Aconitum alkaloids and their metabolites were not detected in urine. CONCLUSIONS: Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits, diffusing from high-content organs (stomach) to other major organs and tissues as well as the heart blood. The main mechanism is the dispersion along the concentration gradient, while urine is not affected by postmortem diffusion, which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.


Subject(s)
Aconitum , Alkaloids , Liver , Tandem Mass Spectrometry , Animals , Rabbits , Aconitum/chemistry , Alkaloids/metabolism , Alkaloids/urine , Alkaloids/analysis , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Liver/metabolism , Kidney/metabolism , Lung/metabolism , Aconitine/analogs & derivatives , Aconitine/pharmacokinetics , Aconitine/urine , Aconitine/metabolism , Aconitine/analysis , Plant Roots/chemistry , Tissue Distribution , Spleen/metabolism , Postmortem Changes , Forensic Toxicology/methods , Myocardium/metabolism , Time Factors , Male
4.
Arthrosc Tech ; 13(4): 102904, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38690354

ABSTRACT

Arthroscopic repair of Bankart injury is the first choice for the treatment of anterior shoulder instability. How to avoid recurring shoulder joint dislocation is a challenge, especially when combined with Hill-Sachs lesions. The arthroscopy technology allows for broader vision and less surgical trauma but is limited by a smaller operating space. At present, extensive descriptions about the surgical procedure of arthroscopic Bankart repair have been published. In this Technical Note, we describe the use of remplissage filling with Hill-Sachs lesion combined with Bankart repair to further improve the surgical accuracy and clinical efficacy. In particular, the application of single needle-assisted outside-in remplissage technique and Bankart repair is introduced in detail.

5.
Cancer Sci ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695305

ABSTRACT

Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced-stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post-surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced-stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field.

6.
Nat Commun ; 15(1): 3995, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734699

ABSTRACT

Optical detection of magnetic field is appealing for integrated photonics; however, the light-matter interaction is usually weak at low field. Here we observe that the photoluminescence (PL) decreases by > 40% at 10 mT in rubrene microcrystals (RMCs) prepared by a capillary-bridge assembly method. The giant magneto-PL (MPL) relies on the singlet-triplet conversion involving triplet-triplet pairs, through the processes of singlet fission (SF) and triplet fusion (TF) during radiative decay. Importantly, the size of RMCs is critical for maximizing MPL as it influences on the photophysical processes of spin state conversion. The SF/TF process is quantified by measuring the prompt/delayed PL with time-resolved spectroscopies, which shows that the geminate SF/TF associated with triplet-triplet pairs are responsible for the giant MPL. Furthermore, the RMC-based magnetometer is constructed on an optical chip, which takes advantages of remarkable low-field sensitivity over a broad range of frequencies, representing a prototype of emerging opto-spintronic molecular devices.

7.
World J Oncol ; 15(3): 482-491, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38751703

ABSTRACT

Background: Peripheral traditional immune cell disorder plays an important role in cancer onset and development. The causal relationships between leukocytes prior to cancer and the risk of digestive system cancer remain unknown. This study assesses the causal correlations between leukocytes and digestive system cancer risk in East Asians and Europeans. Methods: Summary-level data on leukocyte-related genetic variation were extracted from Biobank Japan (107,964 participants) and a recent large-scale meta-analysis (563,946 participants). Summary-level data for the cancers were obtained from Biobank Japan (212,978 individuals) and the FinnGen consortium (178,802 participants). Univariable and multivariable Mendelian randomization (MR) analyses were performed on East Asians and Europeans separately. Results: Univariable MR analysis demonstrated the significant association between circulating eosinophil counts and risk of colorectal cancer (CRC) in East Asians (odds ratio (OR) = 0.80, 95% confidence interval (CI): 0.69 - 0.92, P = 0.002) and a suggestive relationship in the European population (OR = 0.86, 95% CI: 0.77 - 0.97, P = 0.013). An inverse suggestive association was observed between levels of basophils and the risk of gastric cancer (GC) in East Asians (OR = 0.83, 95% CI: 0.72 - 0.97, P = 0.019). The multivariable MR analysis showed the independent causal effect of eosinophil count on CRC risk in East Asians (OR = 0.72, 95% CI: 0.57 - 0.92, P = 0.009) and Europeans (OR = 0.80, 95% CI: 0.70 - 0.92, P = 0.002). Circulating basophils served as the negative causal factor in GC risk in East Asians (OR = 0.80, 95% CI: 0.67 - 0.94, P = 0.007). Conclusions: Our MR analyses revealed a genetic causal relationship between reduced blood eosinophils and an increased CRC risk in both Europeans and East Asians. Furthermore, our results suggested a causal association between decreased basophils and an elevated GC risk specifically in East Asians.

8.
Fitoterapia ; 176: 106007, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38744384

ABSTRACT

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

9.
Antiviral Res ; 226: 105900, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705200

ABSTRACT

BACKGROUND & AIMS: The spread of foot-and-mouth disease virus (FMDV) through aerosol droplets among cloven-hoofed ungulates in close contact is a major obstacle for successful animal husbandry. Therefore, the development of suitable mucosal vaccines, especially nasal vaccines, to block the virus at the initial site of infection is crucial. PATIENTS AND METHODS: Here, we constructed eukaryotic expression plasmids containing the T and B-cell epitopes (pTB) of FMDV in tandem with the molecular mucosal adjuvant Fms-like tyrosine kinase receptor 3 ligand (Flt3 ligand, FL) (pTB-FL). Then, the constructed plasmid was electrostatically attached to mannose-modified chitosan-coated poly(lactic-co-glycolic) acid (PLGA) nanospheres (MCS-PLGA-NPs) to obtain an active nasal vaccine targeting the mannose-receptor on the surface of antigen-presenting cells (APCs). RESULTS: The MCS-PLGA-NPs loaded with pTB-FL not only induced a local mucosal immune response, but also induced a systemic immune response in mice. More importantly, the nasal vaccine afforded an 80% protection rate against a highly virulent FMDV strain (AF72) when it was subcutaneously injected into the soles of the feet of guinea pigs. CONCLUSIONS: The nasal vaccine prepared in this study can effectively induce a cross-protective immune response against the challenge with FMDV of same serotype in animals and is promising as a potential FMDV vaccine.


Subject(s)
Administration, Intranasal , Chitosan , Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease , Nanospheres , Polylactic Acid-Polyglycolic Acid Copolymer , Viral Vaccines , Animals , Chitosan/chemistry , Chitosan/administration & dosage , Foot-and-Mouth Disease Virus/immunology , Foot-and-Mouth Disease Virus/genetics , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Foot-and-Mouth Disease/prevention & control , Foot-and-Mouth Disease/immunology , Mice , Nanospheres/chemistry , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Mice, Inbred BALB C , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female , Nucleic Acids/administration & dosage , Immunity, Mucosal , Drug Delivery Systems
10.
Am J Surg ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38777717

ABSTRACT

BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients. METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs. RESULTS: Of 497 elderly patients, 157 (31.6 â€‹%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 â€‹%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 â€‹% vs. 72.1 â€‹%, P â€‹< â€‹0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 â€‹% confidence interval 1.879-6.198, P â€‹< â€‹0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy. CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.

11.
PLoS One ; 19(5): e0303495, 2024.
Article in English | MEDLINE | ID: mdl-38787821

ABSTRACT

BACKGROUND: Acute respiratory infections (ARIs) have a substantial impact on morbidity, healthcare utilization, and functional decline among older adults. Therefore, we systematically reviewed evidence from randomized controlled trials (RCTs) to evaluate the efficacy and safety of vitamin D supplementation in preventing ARIs in older adults. METHODS: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched until 1 February 2024. RCTs evaluating the use of vitamin D supplements to protect older adults from ARIs were included. Two reviewers independently screened papers, extracted the data and assessed the risk of bias. Data were summarised as relative risks (RRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs). Random effects meta-analyses were used to synthesise the results. GRADE was used to evaluate the quality of evidence. All the analysis were performed with Stata version 17. RESULTS: Twelve trials (41552 participants) were included in the meta-analysis. It showed that vitamin D supplementation probably does not reduce the incidence of ARIs (RR, 0.99; 95% CI, 0.97-1.02, I2 = 0%; moderate certainty). No significant effect of vitamin D supplementation on the risk of ARI was observed for any of the subgroups defined by baseline 25(OH)D concentration, control treatments, dose frequency, study duration, and participants' condition. However, there was a possibility, although not statistically significant, that vitamin D may reduce the risk of ARI in patients with a baseline 25(OH)D concentration <50 nmol/L (OR, 0.90; 95% CI, 0.79-1.04, I2 = 14.7%). Additionally, vitamin D supplements might result in little to no difference in death due to any cause, any adverse event, hypercalcinemia, and kidney stones. CONCLUSIONS: Vitamin D supplementation among older adults probably results in little to no difference in the incidence of ARIs. However, further evidence is needed, particularly for individuals with vitamin D deficiency and populations residing in low and middle income countries. TRIAL REGISTRATION: This study was registered on PROSPERO (CRD42023451265).


Subject(s)
Dietary Supplements , Respiratory Tract Infections , Vitamin D , Humans , Vitamin D/administration & dosage , Vitamin D/therapeutic use , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/drug therapy , Aged , Acute Disease , Randomized Controlled Trials as Topic
12.
Anal Chem ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38810149

ABSTRACT

The retroperitoneal liposarcoma (RLPS) is a rare malignancy whose only curative therapy is surgical resection. However, well-differentiated liposarcomas (WDLPSs), one of its most common types, can hardly be distinguished from normal fat during operation without an effective margin assessment method, jeopardizing the prognosis severely with a high recurrence risk. Here, we combined dual label-free nonlinear optical modalities, stimulated Raman scattering (SRS) microscopy and second harmonic generation (SHG) microscopy, to image two predominant tissue biomolecules, lipids and collagen fibers, in 35 RLPSs and 34 normal fat samples collected from 35 patients. The produced dual-modal tissue images were used for RLPS diagnosis based on deep learning. Dramatically decreasing lipids and increasing collagen fibers during tumor progression were reflected. A ResNeXt101-based model achieved 94.7% overall accuracy and 0.987 mean area under the ROC curve (AUC) in differentiating among normal fat, WDLPSs, and dedifferentiated liposarcomas (DDLPSs). In particular, WDLPSs were detected with 94.1% precision and 84.6% sensitivity superior to existing methods. The ablation experiment showed that such performance was attributed to both SRS and SHG microscopies, which increased the sensitivity of recognizing WDLPS by 16.0 and 3.6%, respectively. Furthermore, we utilized this model on RLPS margins to identify the tumor infiltration. Our method holds great potential for accurate intraoperative liposarcoma detection.

13.
Int J Mol Sci ; 25(9)2024 May 05.
Article in English | MEDLINE | ID: mdl-38732250

ABSTRACT

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.


Subject(s)
Alkaloids , Nitric Oxide , Penicillium , Penicillium/chemistry , Penicillium/metabolism , Mice , Animals , Alkaloids/chemistry , Alkaloids/pharmacology , Alkaloids/isolation & purification , RAW 264.7 Cells , Nitric Oxide/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Nitric Oxide Synthase Type II/metabolism , Molecular Docking Simulation , Lipopolysaccharides , Antioxidants/pharmacology , Antioxidants/chemistry , Molecular Structure
14.
Eur J Oncol Nurs ; 70: 102598, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38795440

ABSTRACT

PURPOSE: This study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients. METHODS: Between December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons. RESULTS: Compared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = -0.32, 95% CI, -0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = -0.11, 95% CI, -0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = -0.05, 95% CI, -0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = -0.66, 95% CI, -0.99 to 0.33, P < 0.001) post-intervention. CONCLUSIONS: Acupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath.


Subject(s)
Acupuncture Therapy , Cough , Lung Neoplasms , Humans , Cough/therapy , Cough/etiology , Lung Neoplasms/complications , Male , Female , Middle Aged , Acupuncture Therapy/methods , Aged , Treatment Outcome , Dyspnea/therapy , Dyspnea/etiology , Adult
15.
Neuroscience ; 548: 39-49, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38697463

ABSTRACT

Chronic inflammatory pain is the highest priority for people with osteoarthritis when seeking medical attention. Despite the availability of NSAIDs and glucocorticoids, central sensitization and peripheral sensitization make pain increasingly difficult to control. Previous studies have identified the ubiquitination system as an important role in the chronic inflammatory pain. Our study displayed that the E3 ubiquitin ligase tripartite motif-containing 14 (Trim14) was abnormally elevated in the serum of patients with osteoarthritis and pain, and the degree of pain was positively correlated with the degree of Trim14 elevation. Furthermore, CFA-induced inflammatory pain rat model showed that Trim14 was significantly increased in the L3-5 spinal dorsal horn (SDH) and dorsal root ganglion (DRG), and in turn the inhibitor of nuclear factor Kappa-B isoform α (IκBα) was decreased after Trim14 elevation. After intrathecal injection of Trim14 siRNA to inhibit Trim14 expression, IκBα expression was reversed and increased, and the pain behaviors and anxiety behaviors of rats were significantly relieved. Overall, these findings suggested that Trim14 may contribute to chronic inflammatory pain by degrading IκBα, and that Trim14 may become a novel therapeutic target for chronic inflammatory pain.


Subject(s)
Chronic Pain , Inflammation , NF-KappaB Inhibitor alpha , Osteoarthritis , Rats, Sprague-Dawley , Signal Transduction , Animals , Male , Osteoarthritis/metabolism , NF-KappaB Inhibitor alpha/metabolism , Humans , Rats , Signal Transduction/physiology , Inflammation/metabolism , Chronic Pain/metabolism , Tripartite Motif Proteins/metabolism , Female , Middle Aged , Ganglia, Spinal/metabolism , Spinal Cord Dorsal Horn/metabolism , Ubiquitin-Protein Ligases/metabolism , Aged
16.
Ecotoxicol Environ Saf ; 279: 116457, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38754198

ABSTRACT

Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.


Subject(s)
Gastrointestinal Microbiome , Methamphetamine , Reproduction , Testis , Animals , Methamphetamine/toxicity , Male , Gastrointestinal Microbiome/drug effects , Mice , Testis/drug effects , Testis/pathology , Reproduction/drug effects , Spermatozoa/drug effects , Mice, Inbred C57BL , Central Nervous System Stimulants/toxicity , Fecal Microbiota Transplantation
17.
J Am Chem Soc ; 146(22): 15576-15586, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38753821

ABSTRACT

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C-H activation constitutes substantial challenges due to the multiple reactivities of strained bicyclic structures. Herein, we develop the domino transformations through an unprecedented cobalt-catalyzed enantioselective C-H activation/nucleophilic [3 + 2] annulation with symmetrical bicyclic alkenes. The methods offer straightforward access to a wide range of chiral molecules bearing [2.2.1]-bridged bicyclic cores with four and five consecutive stereocenters in a single step. Two elaborate salicyloxazoline (Salox) ligands were synthesized based on the rational design and mechanistic understanding. The well-defined chiral pockets generated from asymmetric coordination around the trivalent cobalt catalyst direct the orientation of bicyclic alkenes, leading to excellent enantioselectivity.

18.
Lab Anim (NY) ; 53(6): 136-147, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38773343

ABSTRACT

Cardiovascular disease is a worldwide health problem and a leading cause of morbidity and mortality. Preclinical cardiovascular research using animals is needed to explore potential targets and therapeutic options. Compared with rodents, pigs have many advantages, with their anatomy, physiology, metabolism and immune system being more similar to humans. Here we present an overview of the available pig models for cardiovascular diseases, discuss their advantages over other models and propose the concept of standardized models to improve translation to the clinical setting and control research costs.


Subject(s)
Cardiovascular Diseases , Disease Models, Animal , Animals , Swine
19.
Mater Horiz ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748488

ABSTRACT

The emergence of flexible fabric-based pneumatic actuators (FPAs) with pre-programmable motion capabilities, enhanced security and versatile interaction features significantly advances the construction of sophisticated soft robotic systems, owing to their enhanced security and versatile interaction features. Despite these promising attributes, the commercial viability of FPA products faces a considerable amount of challenges, primarily stemming from the scarcity of highly deformable fabric structures and the availability of industrial fabrication approaches. Taking inspiration from the anisotropic nature of lobster antennae, we propose a scalable and economical strategy to fabricate functional FPAs using nonwoven fabric material with superior mechanical anisotropy. This innovative method involves the adoption of tunable inelastic constrained wires sewn onto extensible nonwoven fabrics with regular wrinkles. This nonwoven fabric-based pneumatic actuator (NFPA) demonstrates specific motion profiles with curvature of over 0.6 cm-1 and output forces of over 140 cN under adjustable pressure conditions. Guided by the constrained wire combinations, NFPA enables diverse programmable motions like spiraling, assistance, and grasping. Furthermore, NFPA incorporated with specific sensors exhibits significant potential in wearable devices with real-time environmental detection for rehabilitation applications. Our work contributes a distinctive insight into the design of programmable NFPAs and enlightens an arena toward versatile soft robotic applications.

20.
Surgery ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38734502

ABSTRACT

BACKGROUND: Despite the Barcelona Clinic Liver Cancer system discouraging hepatectomy for intermediate/advanced hepatocellular carcinoma, the procedure is still performed worldwide, particularly in Asia. This study aimed to develop and validate nomograms for predicting survival and recurrence for these patients. METHODS: We analyzed patients who underwent curative-intent hepatectomy for intermediate/advanced hepatocellular carcinoma between 2010 and 2020 across 3 Chinese hospitals. The Eastern Hepatobiliary Surgery Hospital cohort was used as the training cohort for the nomogram construction, and the Jilin First Hospital and Fujian Mengchao Hepatobiliary Hospital cohorts served as the external validation cohorts. Independent preoperative predictors for survival and recurrence were identified through univariable and multivariable Cox regression analyses. Predictive accuracy was measured using the concordance index and calibration curves. The predictive performance between nomograms and conventional hepatocellular carcinoma staging systems was compared. RESULTS: A total of 1,328 patients met the inclusion criteria. The nomograms for predicting survival and recurrence were developed using 10 and 6 independent variables, respectively. Nomograms' concordance indices in the training cohort were 0.777 (95% confidence interval 0.759-0.800) and 0.719 (95% confidence interval 0.697-0.742) for survival and recurrence, outperforming 4 conventional staging systems (P < .001). Nomograms accurately stratified risk into low, intermediate, and high subgroups. These results were validated well by 2 external validation cohorts. CONCLUSION: We developed and validated nomograms predicting survival and recurrence for patients with intermediate/advanced hepatocellular carcinoma, contradicting Barcelona Clinic Liver Cancer surgical guidelines. These nomograms may facilitate clinicians to formulate personalized surgical decisions, estimate long-term prognosis, and strategize neoadjuvant/adjuvant anti-recurrence therapy.

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