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1.
BMC Pregnancy Childbirth ; 24(1): 390, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802735

ABSTRACT

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.


Subject(s)
Intensive Care Units, Neonatal , Maternal Age , Nomograms , Humans , Female , Pregnancy , Retrospective Studies , Intensive Care Units, Neonatal/statistics & numerical data , Adult , Infant, Newborn , China/epidemiology , Risk Assessment/methods , Logistic Models , Risk Factors , Premature Birth/epidemiology , Patient Admission/statistics & numerical data , Prenatal Diagnosis/methods , Prenatal Diagnosis/statistics & numerical data , East Asian People
2.
BMC Geriatr ; 24(1): 462, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802742

ABSTRACT

BACKGROUND: The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. RESULTS: Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P < 0.001), lower rates of intraoperative transfusion (10.4% vs. 19.0%, P = 0.029), more lymph node harvest (11.0 vs. 10.0, P = 0.014) and shorter postoperative length of stay (LOS) (13.0 vs. 16.0 days, P = 0.013). There were no significant differences in serious complications, reoperation, 90-day readmission and mortality rates (all P > 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. CONCLUSIONS: It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.


Subject(s)
Laparoscopy , Pancreatic Neoplasms , Pancreaticoduodenectomy , Propensity Score , Humans , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/trends , Aged , Male , Female , Laparoscopy/methods , Laparoscopy/adverse effects , Laparoscopy/trends , Retrospective Studies , Pancreatic Neoplasms/surgery , Treatment Outcome , Postoperative Complications/epidemiology , Aged, 80 and over , Time Factors , Length of Stay/trends
3.
Phytomedicine ; 130: 155693, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38763006

ABSTRACT

BACKGROUND: Alcoholic liver disease (ALD), a public health challenge worldwide caused by long-term persistent drinking, is life-threatening with minimal approved therapies. Hepatic steatosis accompanied by inflammation is an initial and inevitable stage in the complex progression of simple alcoholic liver injury to more severe liver diseases such as hepatitis, liver fibrosis, cirrhosis and liver cancer. PURPOSE: We aimed to identify the therapeutic role of Bruceine A (BA) in ALD whilst attempting to explore whether its protective effects depend specifically on the farnesoid X receptor (FXR). METHODS: Autodock was applied to detect the affinity between BA and FXR. Lieber-DeCarli liquid diet with 5 % ethanol (v/v) was adopted to establish the mouse ALD model. The lentivirus mediating FXR (LV-FXR) was injected into mice via the tail vein to establish FXR-overexpressed mice. FXR silencing or overexpression plasmids were transfected into AML-12 cells prior to ethanol stimulation. Quantitative real-time PCR, Western blotting and immunofluorescence assays were employed to determine the expression of related genes. We subjected liver sections to H&E and Oil Red O staining to evaluate the liver histological injury and the deposition of lipid droplets. RESULTS: BA significantly reduced body weight and liver-to-body weight ratios as well as biochemical indexes in mice. Ethanol-induced liver damage and lipid accumulation could be alleviated by BA treatment. BA bound to FXR by two hydrogen bonds. There was a positive correlation between BA administration and FXR expression. BA inhibited the expression of lipid synthesis genes and enhanced the expression of lipid metabolism genes by activating FXR, thus alleviating steatosis in ALD. Moreover, BA exerted an ameliorative effect against inflammation by inhibiting the activation of absent in melanoma 2 (AIM2) inflammasome by activating FXR. FXR overexpression possessed the ability to counter the accumulation of lipid and the activation of AIM2 inflammasome caused by ethanol. FXR deficiency exacerbated ethanol-induced liver steatosis and inflammation. The hepatoprotective effect of BA could be disrupted by FXR antagonist guggulsterone (GS) in vivo and FXR siRNA in vitro. CONCLUSION: BA alleviated alcoholic liver disease by inhibiting AIM2 inflammasome activation through an FXR-dependent mechanism. This study may potentially represent a new therapeutic approach for ALD.

4.
PLoS One ; 19(5): e0303830, 2024.
Article in English | MEDLINE | ID: mdl-38758773

ABSTRACT

In numerous developing nations, the pervasive practice of crop residue incineration is a principal contributor to atmospheric contamination in agricultural operations. This study examines the repercussions of such biomass combustion on air quality during the autumnal harvest season, utilizing data acquired from satellite-based remote sensing of fire events and air pollution measurements. Employing wind direction information alongside difference-in-difference and fixed-effects methodologies, this investigation rectifies estimation inaccuracies stemming from the non-random distribution of combustion occurrences. The empirical findings reveal that agricultural residue burning precipitates an elevation in average PM2.5 and PM10 concentrations by approximately 27 and 22 µg/m3 during the autumnal incineration period, respectively. Furthermore, air pollution attributed to residue burning in prominent grain-producing regions exceeds the national average by approximately 40%. By integrating economic paradigms into agri-environmental inquiries, this study offers novel insights and substantiation of the environmental expenditures engendered by crop residue burning, juxtaposed with extant meteorological and ecological research findings.


Subject(s)
Agriculture , Air Pollution , Crops, Agricultural , Fires , Air Pollution/analysis , Crops, Agricultural/growth & development , Particulate Matter/analysis , Air Pollutants/analysis , Incineration , Environmental Monitoring/methods , Seasons
5.
Insects ; 15(5)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38786859

ABSTRACT

Insects constitute the largest proportion of animals on Earth and act as significant reservoirs and vectors in disease transmission. Rice thrips (Haplothrips aculeatus, family Phlaeothripidae) are one of the most common pests in agriculture. In this study, the full genome sequence of a novel Ollusvirus, provisionally named "Rice thrips ollusvirus 1" (RTOV1), was elucidated using transcriptome sequencing and the rapid amplification of cDNA ends (RACE). A homology search and phylogenetic tree analysis revealed that the newly identified virus is a member of the family Aliusviridae (order Jingchuvirales). The genome of RTOV1 contains four predicted open reading frames (ORFs), including a polymerase protein (L, 7590 nt), a glycoprotein (G, 4206 nt), a nucleocapsid protein (N, 2415 nt) and a small protein of unknown function (291 nt). All of the ORFs are encoded by the complementary genome, suggesting that the virus is a negative-stranded RNA virus. Phylogenetic analysis using polymerase sequences suggested that RTOV1 was closely related to ollusvirus 1. Deep small RNA sequencing analysis reveals a significant accumulation of small RNAs derived from RTOV1, indicating that the virus replicated in the insect. According to our understanding, this is the first report of an Ollusvirus identified in a member of the insect family Phlaeothripidae. The characterisation and discovery of RTOV1 is a significant contribution to the understanding of Ollusvirus diversity in insects.

6.
Arch Dermatol Res ; 316(6): 230, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787441

ABSTRACT

Adult acne vulgaris affects up to 43-51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. "I would use this in the future) and performance ("my skin improved" and "helped my acne clear up faster"). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.


Subject(s)
Acne Vulgaris , Benzoyl Peroxide , Dermatologic Agents , Dicarboxylic Acids , Salicylic Acid , Humans , Acne Vulgaris/drug therapy , Benzoyl Peroxide/administration & dosage , Benzoyl Peroxide/adverse effects , Benzoyl Peroxide/therapeutic use , Adult , Male , Female , Salicylic Acid/administration & dosage , Salicylic Acid/adverse effects , Salicylic Acid/therapeutic use , Prospective Studies , Young Adult , Treatment Outcome , Double-Blind Method , Dicarboxylic Acids/adverse effects , Dicarboxylic Acids/administration & dosage , Dicarboxylic Acids/therapeutic use , Dermatologic Agents/adverse effects , Dermatologic Agents/administration & dosage , Dermatologic Agents/therapeutic use , Vitamin A/administration & dosage , Vitamin A/adverse effects , Vitamin A/therapeutic use , Administration, Cutaneous , Adolescent , Severity of Illness Index , Nonprescription Drugs/administration & dosage , Nonprescription Drugs/adverse effects , Nonprescription Drugs/therapeutic use , Drug Therapy, Combination/methods
7.
Int J Biol Macromol ; 269(Pt 2): 132216, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729483

ABSTRACT

Agricultural by-products of sesame are promising bioresources in food processing. This study extracted lignin from the by-products of sesame oil production, namely, the capsules and straw of black and white sesame. Using acid, alkali, and ethanol methods, 12 distinct lignins were obtained to prepare biochar, aiming to investigate both the structural characteristics of lignin-based biochar (LBB) and its ability to remove benzo[a]pyrene (BaP) from sesame oil. The results showed that white sesame straw was the most suitable raw material for preparing biochar. In terms of the preparation method, acid-extracted lignin biochar was more effective in removing BaP than alkaline or ethanol methods. Notably, WS-1LB (white sesame straw acid-extracted lignin biochar) exhibited the highest BaP adsorption efficiency (91.44 %) and the maximum specific surface area (1065.8187 m2/g), characterized by porous structures. The pseudo 2nd and Freundlich models were found to be the best fit for the adsorption kinetics and isotherms of BaP on LBB, respectively, suggesting that a multilayer adsorption process was dominant. The high adsorption of LBB mainly resulted from pore filling. This study provides an economical and highly efficient biochar adsorbent for the removal of BaP in oil.


Subject(s)
Charcoal , Lignin , Sesame Oil , Lignin/chemistry , Charcoal/chemistry , Adsorption , Sesame Oil/chemistry , Benzo(a)pyrene/chemistry , Kinetics
8.
Adv Sci (Weinh) ; : e2400692, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783578

ABSTRACT

Primate-specific DAZ (deleted in azoospermia) has evolved in the azoospermia factor c (AZFc) locus on the Y chromosome. Loss of DAZ is associated with azoospermia in patients with deletion of the AZFc region (AZFc_del). However, the molecular mechanisms of DAZ in spermatogenesis remain uncertain. In this study, the molecular mechanism of DAZ is identified, which is unknown since it is identified 40 years ago because of the lack of a suitable model. Using clinical samples and cell models, it is shown that DAZ plays an important role in spermatogenesis and that loss of DAZ is associated with defective proliferation of c-KIT-positive spermatogonia in patients with AZFc_del. Mechanistically, it is shown that knockdown of DAZ significantly downregulated global translation and subsequently decreased cell proliferation. Furthermore, DAZ interacted with PABPC1 via the DAZ repeat domain to regulate global translation. DAZ targeted mRNAs that are involved in cell proliferation and cell cycle phase transition. These findings indicate that DAZ is a master translational regulator and essential for the maintenance of spermatogonia. Loss of DAZ may result in defective proliferation of c-KIT-positive spermatogonia and spermatogenic failure.

9.
J Phys Chem Lett ; 15(14): 3929-3937, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38568181

ABSTRACT

Triangulene, as a typical open-shell graphene fragment, has attracted widespread attention for nanospintronics, promising to serve as building blocks in spin-logic units. Here, using ab initio calculations, we systematically study the laser-induced ultrafast spin-dynamic processes on triangulene nanoflakes, decorated with a transition-metal atom. The results reveal a competition between the induced magnetic center and the carbon edge of the triangulene, resulting in the coexistence of dual spin-density-distribution patterns on such single-magnetic-center systems, thus opening up possibilities of complex spin-dynamic scenarios beyond the spin flip. Interestingly, no matter what direction the spin points to, it is possible to achieve reversible spin-transfer processes using the same laser pulse. Increasing the pool of elementary processes to contain not only spin-direction-dependent but also spin-direction-independent scenarios allows for more versatile spin-logic operations, including classical handling of information and quantum computing. In the present work, we suggest downscaling nanospintronic devices by integrating triangulene-based nanostructures.

10.
Emerg Microbes Infect ; 13(1): 2341142, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38581279

ABSTRACT

H6N6 avian influenza viruses (AIVs) have been widely detected in wild birds, poultry, and even mammals. Recently, H6N6 viruses were reported to be involved in the generation of H5 and H7 subtype viruses. To investigate the emergence, evolutionary pattern, and potential for an epidemic of H6N6 viruses, the complete genomes of 198 H6N6 viruses were analyzed, including 168 H6N6 viruses deposited in the NCBI and GISAID databases from inception to January 2019 and 30 isolates collected from China between November 2014 and January 2019. Using phylogenetic analysis, the 198 strains of H6N6 viruses were identified as 98 genotypes. Molecular clock analysis indicated that the evolution of H6N6 viruses in China was constant and not interrupted by selective pressure. Notably, the laboratory isolates reassorted with six subtype viruses: H6N2, H5N6, H7N9, H5N2, H4N2, and H6N8, resulting in nine novel H6N6 reassortment events. These results suggested that H6N6 viruses can act as an intermediary in the evolution of H5N6, H6N6, and H7N9 viruses. Animal experiments demonstrated that the 10 representative H6N6 viruses showed low pathogenicity in chickens and were capable of infecting mice without prior adaptation. Our findings suggest that H6N6 viruses play an important role in the evolution of AIVs, and it is necessary to continuously monitor and evaluate the potential epidemic of the H6N6 subtype viruses.


Subject(s)
Chickens , Evolution, Molecular , Genome, Viral , Influenza A virus , Influenza in Birds , Phylogeny , Reassortant Viruses , Animals , China/epidemiology , Reassortant Viruses/genetics , Reassortant Viruses/classification , Reassortant Viruses/isolation & purification , Influenza in Birds/virology , Influenza in Birds/epidemiology , Mice , Chickens/virology , Influenza A virus/genetics , Influenza A virus/classification , Influenza A virus/isolation & purification , Genotype , Humans
11.
Biotechnol Bioeng ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634289

ABSTRACT

L-cysteine is an important sulfur-containing amino acid being difficult to produce by microbial fermentation. Due to the lack of high-throughput screening methods, existing genetically engineered bacteria have been developed by simply optimizing the expression of L-cysteine-related genes one by one. To overcome this limitation, in this study, a biosensor-based approach for multilevel biosynthetic pathway optimization of L-cysteine from the DecR regulator variant of Escherichia coli was applied. Through protein engineering, we obtained the DecRN29Y/C81E/M90Q/M99E variant-based biosensor with improved specificity and an 8.71-fold increase in dynamic range. Using the developed biosensor, we performed high-throughput screening of the constructed promoter and RBS combination library, and successfully obtained the optimized strain, which resulted in a 6.29-fold increase in L-cysteine production. Molecular dynamics (MD) simulations and electrophoretic mobility shift analysis (EMSA) showed that the N29Y/C81E/M90Q/M99E variant had enhanced induction activity. This enhancement may be due to the increased binding of the variant to DNA in the presence of L-cysteine, which enhances transcriptional activation. Overall, our biosensor-based strategy provides a promising approach for optimizing biosynthetic pathways at multiple levels. The successful implementation of this strategy demonstrates its potential for screening improved recombinant strains.

12.
J Glob Health ; 14: 04066, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38574355

ABSTRACT

Background: Neck pain has become very common in China and has greatly affected individuals, families, and society in general. In this study, we aimed to report on the rates and trends of the prevalence, incidence, and years lived with disability (YLDs) caused by neck pain in the general population of China from 1990 to 2019. Methods: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) study to estimate the number and age standardised rates per 100 000 population of neck pain point prevalence, annual incidence, and YLDs in 33 provinces/municipalities/autonomous regions of China, stratified by age, sex, and sociodemographic index (SDI) from 1990 to 2019. We then compared these estimates with other G20 countries. Results: There were 6.80 × 107 patients with neck pain in 2019, presenting an increase from 3.79 × 107 in 1990. Likewise, the national age-standardised point prevalence increased slightly from 3.53% in 1990 to 3.57% in 2019. The YLDs increased by 78.08%, from 3814 × 103 in 1990 to 6792 × 103 in 2019. The age-standardised YLDs rate increased 1.50% from 352.84 in 1990 to 358.10 in 2019. The point prevalence of neck pain in 2019 was higher in females compared with males. These estimates were all above the global average level and increased more rapidly among G20 countries from 1990 to 2019. We generally observed a positive association between age-standardised YLD rates for neck pain and SDI, suggesting the burden is higher at higher sociodemographic indices. Conclusions: Neck pain is a serious public health problem in the general population in China, especially in its central and western regions, with an overall increasing trend in the last three decades. This is possibly related to changes of people's lifestyles and work patterns due to improvements in societal well-being and technology. Raising awareness of risk factors for neck pain in the general population and establishing effective preventive and treatment strategies could help reduce the future burden of neck disorders.


Subject(s)
Disabled Persons , Global Burden of Disease , Male , Female , Humans , Neck Pain/epidemiology , Prevalence , Incidence , China/epidemiology , Global Health
13.
Micromachines (Basel) ; 15(4)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38675358

ABSTRACT

Laser-processing technology has been widely used in the ultra-precision machining of diamond materials. It has the advantages of high precision and high efficiency, especially in the field of super-hard materials and high-precision parts manufacturing. This paper explains the fundamental principles of diamond laser processing, introduces the interaction mechanisms between various types of lasers and diamond materials, focuses on analyzing the current development status of various modes of laser processing of diamond, briefly discusses the relevant applications in diamond cutting, micro-hole forming, and micro-groove machining, etc., and finally discusses the issues, challenges, and potential future advancements of laser technology in the field of diamond processing at this point.

14.
Talanta ; 274: 125976, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38579417

ABSTRACT

Hypoxia is commonly regarded as a typical feature of solid tumors, which originates from the insufficient supply of oxygen. Herein, the development of an efficient method for assessing hypoxia levels in tumors is strongly desirable. Nitroreductase (NTR) is an overexpressed reductase in the solid tumors, has been served as a potential biomarker to evaluate the degrees of hypoxia. In this work, we elaborately synthesized a new near-infrared (NIR) fluorescence probe (MR) to monitor NTR activity for assessment of hypoxia levels in living cells and in tumors. Upon exposure of NTR, the nitro-unit of MR could be selectively reduced to amino-moiety with the help of nicotinamide adenine dinucleotide. Moreover, the obtained fluorophore emitted a prominent NIR fluorescence, because it possessed a classical "push-pull" structure. The MR displayed several distinguished characters toward NTR, including intense NIR fluorescent signals, large Stokes shift, high selectivity and low limit of detection (46 ng/mL). Furthermore, cellular confocal fluorescence imaging results validated that the MR had potential of detecting NTR levels in hypoxic cells. Significantly, using the MR, the elevated of NTR levels were successfully visualized in the tumor-bearing mouse models. Therefore, this detecting platform based on this probe may be tactfully constructed for monitoring the variations of NTR and estimating the degrees of hypoxia in tumors.


Subject(s)
Fluorescent Dyes , Nitroreductases , Nitroreductases/metabolism , Nitroreductases/analysis , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Animals , Mice , Humans , Optical Imaging/methods , Infrared Rays , Mice, Nude , Mice, Inbred BALB C , Neoplasms/diagnostic imaging , Neoplasms/metabolism
15.
CNS Neurosci Ther ; 30(4): e14696, 2024 04.
Article in English | MEDLINE | ID: mdl-38668740

ABSTRACT

AIMS: Excessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio-sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown. METHODS: Real-time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5-Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF-κB signaling pathway was explored through immunofluorescence staining, western blot, co-immunoprecipitation and proximity ligation assay. RESULTS: The level of pro-inflammation cytokines and activation of NF-κB signaling pathway was suppressed by AZD1390 in vitro and in vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF-κB (NEMO) in an ATM-dependent and ATM-independent way respectively, which reduced the activation of the NF-κB pathway. CONCLUSION: AZD1390 suppressed NF-κB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke.


Subject(s)
Microglia , Neuroinflammatory Diseases , Pyridines , Quinolones , Animals , Microglia/drug effects , Microglia/metabolism , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Male , Mice , Mice, Inbred C57BL , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors , NF-kappa B/metabolism , NF-kappa B/antagonists & inhibitors , Cytokines/metabolism , Signal Transduction/drug effects
16.
Toxicol Appl Pharmacol ; 486: 116947, 2024 May.
Article in English | MEDLINE | ID: mdl-38688426

ABSTRACT

AIMS: SERCA2, one of the P-type pumps encoded by gene ATP2A2, is the only calcium reflux channel of the endoplasmic reticulum (ER) and participates in maintaining calcium homeostasis. The present study was designed to explore SERCA2 expression pattern in auditory hair cells and the possible mechanism underlying the effects of SERCA2 on cisplatin-induced ototoxicity. MAIN METHODS: The SERCA2 expression pattern in cochlea hair cells and HEI-OC1 cells was measured by Western blot (WB) and immunofluorescence staining. The apoptosis and its related factors were detected by TUNEL assay and WB. The expression levels of ER stress-related factors, ATF6, PERK, IRE1α, and GRP78, were measured via WB. As for the determination of SERCA2 overexpression and knockdown, plasmids and lentiviral vectors were constructed, respectively. KEY FINDINGS: We found that SERCA2 was highly expressed in cochlea hair cells and HEI-OC1 cells. Of note, the level of SERCA2 expression in neonatal mice was remarkably higher than that in adult mice. Under the exposure of 30 µM cisplatin, SERCA2 was down-regulated significantly compared with the control group. In addition, cisplatin administration triggered the occurrence of ER stress and apoptosis. Those events were reversed by overexpressing SERCA2. On the contrary, SERCA2 knockdown could aggravate the above processes. SIGNIFICANCE: The findings from the present study disclose, for the first time, that SERCA2 is abundantly expressed in cochlea hair cells, and the suppression of SERCA2 caused by cisplatin could trigger ER homeostasis disruption, thereby implying that SERCA2 might be a promising target to prevent cisplatin-induced cytotoxicity of hair cells.


Subject(s)
Apoptosis , Cisplatin , Endoplasmic Reticulum Chaperone BiP , Endoplasmic Reticulum Stress , Hair Cells, Auditory , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Cisplatin/toxicity , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Animals , Endoplasmic Reticulum Stress/drug effects , Mice , Apoptosis/drug effects , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/metabolism , Hair Cells, Auditory/pathology , Cell Line , Antineoplastic Agents/toxicity , Male , Ototoxicity/prevention & control
17.
Digit Biomark ; 8(1): 40-51, 2024.
Article in English | MEDLINE | ID: mdl-38606345

ABSTRACT

Introduction: Cervical spine disease is a leading cause of pain and disability. Degenerative conditions of the spine can result in neurologic compression of the cervical spinal cord or nerve roots and may be surgically treated with an anterior cervical discectomy and fusion (ACDF) in up to 137,000 people per year in the United States. A common sequelae of ACDF is reduced cervical range of motion (CROM) with patient-based complaints of stiffness and neck pain. Currently, tools for assessment of CROM are manual, subjective, and only intermittently utilized during doctor or physical therapy visits. We propose a skin-mountable acousto-mechanic sensor (ADvanced Acousto-Mechanic sensor; ADAM) as a tool for continuous neck motion monitoring in postoperative ACDF patients. We have developed and validated a machine learning neck motion classification algorithm to differentiate between eight neck motions (right/left rotation, right/left lateral bending, flexion, extension, retraction, protraction) in healthy normal subjects and patients. Methods: Sensor data from 12 healthy normal subjects and 5 patients were used to develop and validate a Convolutional Neural Network (CNN). Results: An average algorithm accuracy of 80.0 ± 3.8% was obtained for healthy normal subjects (94% for right rotation, 98% for left rotation, 65% for right lateral bending, 87% for left lateral bending, 89% for flexion, 77% for extension, 50% for retraction, 84% for protraction). An average accuracy of 67.5 ± 5.8% was obtained for patients. Discussion: ADAM, with our algorithm, may serve as a rehabilitation tool for neck motion monitoring in postoperative ACDF patients. Sensor-captured vital signs and other events (extubation, vocalization, physical therapy, walking) are potential metrics to be incorporated into our algorithm to offer more holistic monitoring of patients after cervical spine surgery.

18.
Sci Rep ; 14(1): 8072, 2024 04 05.
Article in English | MEDLINE | ID: mdl-38580712

ABSTRACT

There have been over 769 million cases of COVID-19, and up to 50% of infected individuals are asymptomatic. The purpose of this study aimed to assess the use of a clinical-grade physiological wearable monitoring system, ANNE One, to develop an artificial intelligence algorithm for (1) cough detection and (2) early detection of COVID-19, through the retrospective analysis of prospectively collected physiological data from longitudinal wear of ANNE sensors in a multicenter single arm study of subjects at high risk for COVID-19 due to occupational or home exposures. The study employed a two-fold approach: cough detection algorithm development and COVID-19 detection algorithm development. For cough detection, healthy individuals wore an ANNE One chest sensor during scripted activity. The final performance of the algorithm achieved an F-1 score of 83.3% in twenty-seven healthy subjects during biomarker validation. In the COVID-19 detection algorithm, individuals at high-risk for developing COVID-19 because of recent exposures received ANNE One sensors and completed daily symptom surveys. An algorithm analyzing vital parameters (heart rate, respiratory rate, cough count, etc.) for early COVID-19 detection was developed. The COVID-19 detection algorithm exhibited a sensitivity of 0.47 and specificity of 0.72 for detecting COVID-19 in 325 individuals with recent exposures. Participants demonstrated high adherence (≥ 4 days of wear per week). ANNE One shows promise for detection of COVID-19. Inclusion of respiratory biomarkers (e.g., cough count) enhanced the algorithm's predictive ability. These findings highlight the potential value of wearable devices in early disease detection and monitoring.


Subject(s)
COVID-19 , Wearable Electronic Devices , Humans , Algorithms , Artificial Intelligence , Cough/diagnosis , COVID-19/diagnosis , COVID-19 Testing , Polymerase Chain Reaction , Retrospective Studies
19.
J Mater Chem B ; 12(17): 4080-4096, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38577851

ABSTRACT

Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal-organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand-receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal-organic frameworks (MOFs) as camouflaged nanocarriers.


Subject(s)
Biomimetic Materials , Metal-Organic Frameworks , Neoplasms , RNA, Small Interfering , Metal-Organic Frameworks/chemistry , RNA, Small Interfering/chemistry , Humans , Biomimetic Materials/chemistry , Neoplasms/therapy , Neoplasms/drug therapy , Animals , Drug Carriers/chemistry , Biomimetics
20.
Sci Rep ; 14(1): 7334, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38538843

ABSTRACT

Wetting and evaporation behavior of dilute sodium dodecyl sulfate (SDS) droplets on planar polydimethylsiloxane (PDMS) surfaces under a direct current (DC) electric field were experimentally investigated. Two characteristic voltages-actuation voltage and saturation voltage were observed in the electrowetting of dilute SDS droplets on PDMS surfaces. It was found that for dilute SDS droplets with a fixed SDS concentration substrate elasticity has an obvious influence on actuation voltage, and saturation voltage increased with the increase of mass ratio of PDMS surfaces. SDS concentration was also found to obviously influence actuation voltage and saturation voltage when SDS concentration was in a certain range. For the case of evaporation of sessile dilute SDS droplets on PDMS surfaces with the application of a DC electric field, substrate elasticity, SDS concentration and the magnitude of applied voltage were all found to have an influence on the duration of CCR stage. Moreover, contact angle hysteresis for dilute SDS droplets on a planar PDMS 10:1 surface under different applied voltage was measured and it was found that the magnitude of applied voltage greatly influenced contact angle hysteresis, which also depends on SDS concentration and KCl concentration.

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