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The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.
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Biodegradación Ambiental , Microplásticos , Hidrocarburos Policíclicos Aromáticos , Polietileno , Microbiología del Suelo , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/análisis , Suelo/química , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/crecimiento & desarrollo , Bacterias/efectos de los fármacos , Oxígeno/metabolismoRESUMEN
Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.
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The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.
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Gastritis , Aprendizaje Automático , Metaplasia , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Metaplasia/patología , Gastritis/patología , Gastritis/diagnóstico , Técnicas Biosensibles/métodos , Jugo Gástrico/química , Neoplasias Gástricas/patología , Neoplasias Gástricas/diagnóstico , Enfermedad Crónica , AlgoritmosRESUMEN
Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.
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AIM: The paradoxical protective association between overweight/obesity and diabetic microvascular complications (DMC), a phenomenon well-known as the obesity paradox, has been considered a non-causal association based on methodological influences. We aimed to investigate the association of generalized and abdominal obesity, as measured by body mass index (BMI) and waist circumference (WC), respectively, with DMC in patients with type 2 diabetes (T2D), using a causal inference approach. MATERIALS AND METHODS: We enrolled 1436 patients with clinically diagnosed T2D but not DMC at baseline in a community-based prospective cohort in China between 2017 and 2019 and followed them annually until 2022 with new-onset DMC recorded. Marginal structural Cox models with inverse probability weighting were constructed to determine the causal association. Subgroup analyses were performed to identify potential effect modifiers. RESULTS: We observed 360 incident DMC cases, including 109 cases of diabetic nephropathy (DN) and 277 cases of diabetic retinopathy (DR) during four follow-up visits. Multivariable-adjusted hazard ratios (95% confidence intervals) for overall DMC, DN and DR were 1.037 (1.005-1.071), 1.117 (1.062-1.175) and 1.018 (0.980-1.059) for 1 kg/m2 increase in BMI, and 1.005 (0.994-1.017), 1.034 (1.018-1.051) and 1.000 (0.987-1.014) for 1 cm increase in WC, respectively. Similar patterns were observed across the BMI and WC categories, while the positive association appeared to be more pronounced in women. CONCLUSIONS: Generalized but not abdominal obesity was associated with an increased risk for the overall DMC, whereas both obesities were causally related to DN, albeit not DR, in T2D. Routine weight management should not be neglected in diabetes care, particularly in women.
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Diabetes Mellitus Tipo 2 , Angiopatías Diabéticas , Obesidad Abdominal , Obesidad , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Angiopatías Diabéticas/epidemiología , Angiopatías Diabéticas/etiología , Anciano , China/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Índice de Masa Corporal , Circunferencia de la Cintura , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Factores de Riesgo , Adulto , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/complicaciones , IncidenciaRESUMEN
Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.
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Herbivorous insects have evolved metabolic strategies to survive the challenges posed by plant secondary metabolites (SMs). This study reports an exploration of SMs present in pears, which serve as a defense against invasive Cydia pomonella and native Grapholita molesta and their counter-defense response. The feeding preferences of fruit borers are influenced by the softening of two pear varieties as they ripen. The content of SMs, such as quercetin and rutin, increases due to feeding by fruit borers. Notably, quercetin levels only increase after C. pomonella feeding. The consumption of SMs affects the growth of fruit borer population differently, potentially due to the activation of P450 genes by SMs. These two fruit borers are equipped with specific P450 enzymes that specialize in metabolizing quercetin and rutin, enabling them to adapt to these SMs in their host fruits. These findings provide valuable insights into the coevolution of plants and herbivorous insects.
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BACKGROUND: The metabolic score for insulin resistance (METS-IR) has emerged as a noninsulin-based index for the approximation of insulin resistance (IR), yet longitudinal evidence supporting the utility of METS-IR in the primary prevention of type 2 diabetes mellitus (T2DM) remains limited. OBJECTIVE: We aimed to investigate the longitudinal association between METS-IR, which combines fasting plasma glucose (FPG), lipid profiles, and anthropometrics that can be routinely obtained in resource-limited primary care settings, and the incidence of new-onset T2DM. METHODS: We conducted a closed-cohort analysis of a nationwide, prospective cohort of 7583 Chinese middle-aged and older adults who were free of T2DM at baseline, sampled from 28 out of 31 provinces in China. We examined the characteristics of participants stratified by elevated blood pressure (BP) at baseline and new-onset T2DM at follow-up. We performed Cox proportional hazard regression analysis to explore associations of baseline METS-IR with incident T2DM in participants overall and in participants stratified by baseline BP. We also applied net reclassification improvement and integrated discrimination improvement to examine the incremental value of METS-IR. RESULTS: During a mean follow-up period of 6.3 years, T2DM occurred in 527 participants, among which two-thirds (332/527, 62.9%; 95% CI 58.7%-67.1%) had baseline FPG<110 mg/dL. A SD unit increase in baseline METS-IR was associated with the first incidence of T2DM (adjusted hazard ratio [aHR] 1.33, 95% CI 1.22-1.45; P<.001) in all participants. We obtained similar results in participants with normal baseline BP (aHR 1.41, 95% CI 1.22-1.62; P<.001) and elevated baseline BP (aHR 1.29, 95% CI 1.16-1.44; P<.001). The predictive capability for incident T2DM was improved by adding METS-IR to FPG. In study participants with new-onset T2DM whose baseline FPG was <126 mg/dL and <110 mg/dL, 62.9% (332/527; 95% CI 60%-65.9%) and 58.1% (193/332; 95% CI 54.3%-61.9%) of participants had baseline METS-IR above the cutoff values, respectively. CONCLUSIONS: METS-IR was significantly associated with new-onset T2DM, regardless of baseline BP level. Regular monitoring of METS-IR on top of routine blood glucose in clinical practice may add to the ability to enhance the early identification of primary care populations at risk for T2DM.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Atención Primaria de Salud , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Persona de Mediana Edad , Femenino , Masculino , Estudios Prospectivos , Atención Primaria de Salud/estadística & datos numéricos , China/epidemiología , Anciano , Incidencia , Factores de Riesgo , Glucemia/análisisRESUMEN
The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.
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Estimulantes del Sistema Nervioso Central , Metilfenidato , Ratas , Animales , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Ratas Endogámicas SHR , Dopamina , Ratas Endogámicas WKY , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Estimulantes del Sistema Nervioso Central/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The reactive oxygen species (ROS) surge in the chronic wound tissue of diabetic ulcers (DUs) aggravates the inflammatory response. The oxidative stress state during inflammation will exacerbate inflammation and cause tissue damage, resulting in prolonged wound healing. Shengjihuayu Formula (SJHYF) is a renowned Chinese medicine prescription for treating chronic wounds in diabetic ulcers. Growing clinical evidence has demonstrated that SJHYF exhibits superior therapeutic efficacy and has a favorable safety profile. However, the underlying mechanisms by which SJHYF ameliorates oxidative damage under pathological conditions of DUs remain unclear. OBJECTIVE: To investigate the cytoprotective properties of SJHYF on hydrogen peroxide (H2O2)-induced cell damage in human HaCaT keratinocytes and to explore its potential targets and molecular pathways in treating DUs using RNA-seq. METHODS: HaCaT cells were incubated with H2O2 for 24 h to construct an oxidative stress cell model. Cell viability and proliferation were measured using the MTT and EdU assays, respectively. Cell migration was assessed using the scratch assay, and the fluorescence intensity of ROS was measured using the DCFH-DA probe. The chemical components of SJHYF were analyzed by UPLC-Q-TOF/MS, while the therapeutic effects of SJHYF on H2O2-induced HaCaT cells were analyzed using RNA-Seq. The potential target genes were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). At the same time, the pathway phenotype expression of SJHYF on the protection of H2O2-induced HaCaT cells was explored using Western Blot. RESULTS: The application of SJHY at a concentration of 0.25 mg/mL promoted cell proliferation, cell migration, and reduced ROS production. In addition, SJHYF was detected to have a total of 93 active compounds, including key components such as Galloyl-beta-D-glucose, Danshensu, Procyanidin B2, Catechin, and Alkannin. The RNA-seq analysis identified several core targets namely KRT17, TGM1, JUNB, PRDX5, TXNIP, PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs pathway and its related transcription factors. CONCLUSION: SJHYF displays significant protective effects on H2O2-induced oxidative cell damage in HaCaT cells via blocking the JNK/c-Jun/MMPs pathway.
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Diabetes Mellitus , Glucosa , Peróxido de Hidrógeno , Humanos , Especies Reactivas de Oxígeno/metabolismo , Peróxido de Hidrógeno/metabolismo , Úlcera , Estrés Oxidativo , Queratinocitos , Sistema de Señalización de MAP Quinasas , Inflamación/metabolismo , Diabetes Mellitus/metabolismo , ApoptosisRESUMEN
BACKGROUND: Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. OBJECTIVE: This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. METHODS: This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. RESULTS: The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariableadjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). CONCLUSIONS: Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Obesidad Abdominal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/epidemiología , Estudios Prospectivos , Anciano , ChinaRESUMEN
OBJECTIVES: To elucidate the characteristics of a colistin-resistant and hypervirulent Klebsiella quasipneumoniae subsp. similipneumoniae strain (KP8) using whole genome sequencing and various phenotypic assays. METHODS: Antimicrobial susceptibility testing was performed using broth microdilution. Whole genome sequencing and comparative genomics were utilised to elucidate genomic characteristics. Phenotypic assays to evaluate virulence factors included measurements of mucosal viscosity, biofilm production, siderophore production, infection of A549 cells, serum-killing assays, and Galleria mellonella infection models. RESULTS: Whole-genome sequencing revealed that the strain (KP8) belongs to sequence type 367 (ST367) and capsular type 1 (KL1), and it harbours several virulence genes, including regulator of mucoid phenotype (rmpA/A2), salmochelin (iroBCDN) and aerobactin (iucABCDiutA). Antibiotic susceptibility tests showed that KP8 was resistant to colistin. Genome analysis showed that the colistin resistance of KP8 might be related to amino acid insertions in pmrB (L215_D217, insL) and pagP (M1_S3, insV). Importantly, KP8 demonstrated comparable mucosal viscosity, biofilm production capacity, siderophore production levels to hvKP. Serum-killing experiments, A549 cell infection models, and G. mellonella infection models further indicated that KP8 displayed high virulence, akin to the hypervirulent strain NUTH-K2044. Notably, global genome analysis of the K. quasipneumoniae subsp. similipneumoniae strains highlighted that the ST367 lineage has a higher tendency to carry virulence-associated genes compared to other sequence types. The prevalence of virulence-associated factors concentrated within Chinese ST367 isolates reinforces this observation. CONCLUSION: These findings further enhance our understanding of the resistance and pathogenicity of ST367 K. quasipneumoniae subsp. similipneumoniae strain and also providing a broader perspective on the global epidemiological landscape.
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Colistina , Infecciones por Klebsiella , Humanos , Colistina/farmacología , Infecciones por Klebsiella/epidemiología , Klebsiella/genética , Factores de Virulencia/genética , SideróforosRESUMEN
BACKGROUND/PURPOSE: Zirconia has been a popular material in dental implantology with good biocompatibility. But few research focused on its application in implant drills. This study aimed to investigate the physical, thermal, and biological effects on using the zirconia and stainless-steel drills for implant bone site preparation. METHODS: We performed a series of experiments to evaluate the physical wearing properties of zirconia and stainless-steel drills of identical diameter and similar shape. During the implant site preparation thermal test, we subjected both drills onto a resin-embedded bone, utilizing a thermal couple device without irrigation. Moreover, we conducted a cell study by collecting bone cells in vivo while preparing the implant site with both tested drills. The cell activity was evaluated through cell proliferation colorimetric analysis (XTT) and alkaline phosphatase (ALP) activity measurements. RESULTS: The zirconia drill outperforms the stainless-steel drill in terms of requiring less force, maintaining stability over repeated cutting tests, and generating lower temperatures during drilling (stainless-steel drill: 45.48 ± 1.31 °C; zirconia-coated drill: 32.98 ± 1.21 °C, P = 0.000247). Meanwhile, both types of drills show similar results in XTT colorimetric analysis and ALP activity test. CONCLUSION: The thermal effect study is more favorable for using the zirconia drill than the stainless-steel drill for bone preparation. Cytological analysis indicate that the zirconia drill produces a similar impact on bone cells activity as the stainless-steel drill. Therefore, we conclude that the zirconia drills offer a good cutting effect similar to currently available stainless-steel drills in various aspects.
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OBJECTIVES: Chronic rhinosinusitis (CRS) reduces the health-related quality of life and subsequently causes a tremendous socio-economic impact. Although many studies have been conducted, few have identified a relationship between bacteriological characteristics and different phenotypes or endotypes. Therefore, this study aimed to elucidate the recent trends in bacterial cultures from different types of CRS in the Asian population. METHODS: This retrospective case-control study recruited patients diagnosed with CRS who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into those with chronic rhinosinusitis with nasal polyps (CRSwNP)/chronic rhinosinusitis without nasal polyps (CRSsNP), eosinophilic chronic rhinosinusitis (eCRS)/non-eosinophilic chronic rhinosinusitis (NECRS), and central compartment atopic disease (CCAD)/lateral-dominant nasal polyp (LDNP) groups. The demographic data and bacteriological characteristics of the groups were analyzed. RESULTS: We included 503 patients, identifying no significant difference between CRSwNP and CRSsNP for several common bacteria in CRS. The number of Staphylococcus epidermidis isolates in culture was significantly higher in the NECRS group (50.46% vs. 32.56%, p = 0.0003) than that in the eCRS group. The number of methicillin-resistant Staphylococcus aureus (MRSA; 8.51% vs. 2.35%, p = 0.0221) positive isolates was significantly higher in the CCAD group than that in the LDNP group. CONCLUSIONS: This was the first study in Asia to analyze the relationship between bacteriological characteristics and CCAD. MRSA is significantly higher in the CCAD group than that in the LDNP group. Recognizing the unique microbiology of CRSwNP, eCRS, and CCAD is crucial when selecting antimicrobial therapy to lessen the socio-economic impact. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1071-1076, 2024.
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Bacteriología , Staphylococcus aureus Resistente a Meticilina , Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Pólipos Nasales/complicaciones , Pólipos Nasales/cirugía , Pólipos Nasales/diagnóstico , Calidad de Vida , Rinitis/diagnóstico , Fenotipo , Sinusitis/diagnóstico , Enfermedad CrónicaRESUMEN
Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC50 values were 4.7 and 6.4 µM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg-1·d-1, i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers.
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Piridinas , Pironas , Neoplasias Gástricas , Sulfonamidas , Humanos , Animales , Ratones , Neoplasias Gástricas/patología , Línea Celular Tumoral , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Células Madre Neoplásicas , Apoptosis , Serina Endopeptidasas/metabolismoRESUMEN
While previous studies have reported G protein-coupled receptor (GPCR)-mediated insecticide resistance in various arthropods, the understanding of GPCR-associated resistance mechanisms in Cydia pomonella remains limited. In this study, a total of 95 CpGPCR genes categorized into four families were identified in C. pomonella. Results revealed high expression levels of the majority of the CpGPCRs during the first larval stage and in the head of C. pomonella. Exposure to lambda-cyhalothrin significantly increased the expression of 15 CpGPCRs, including CpGPCR70, which is highly expressed in all larval stages and shows the highest expression in the midgut. RNA interference (RNAi) demonstrated that downregulation of CpGPCR70 leads to reduced expression of key resistance-related genes and a decreased tolerance of larvae to lambda-cyhalothrin. These findings indicate that CpGPCR70 plays a crucial role in regulating the expression of detoxifying genes involved in lambda-cyhalothrin resistance, offering valuable insights for the development of more effective pest control strategies.
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Insecticidas , Mariposas Nocturnas , Piretrinas , Humanos , Animales , Piretrinas/farmacología , Piretrinas/metabolismo , Mariposas Nocturnas/metabolismo , Nitrilos/farmacología , Nitrilos/metabolismo , Larva , Insecticidas/farmacología , Insecticidas/metabolismoRESUMEN
The advantageous characteristics of invasive pests, particularly their ability to reproduce and adapt to the environment, have been observed. However, it remains unclear what specific inherent superiority enables fruit pests to successfully invade and dominate in interactions with other species. In this study, we report that Cydia pomonella (Linnaeus), a notorious invasive pest of pome fruits and walnuts globally, employs unique reproductive strategies in response to quercetin, a plant compound in host fruits. By monitoring adult dynamics and fruit infestation rates, we observed a competitive relationship between C. pomonella and the native species Grapholita molesta (Busck). C. pomonella was able to occupy vacant niches to ensure its population growth. We also found that quercetin had different effects on the reproductive capacity and population growth of C. pomonella and G. molesta. While quercetin stimulated the fecundity and population growth of G. molesta, it inhibited C. pomonella. However, C. pomonella was able to rapidly increase its population after exposure to quercetin by adopting an 'accelerated burst' of oviposition strategy, with each individual making a greater reproductive contribution compared to the control. We further demonstrated that the effect of quercetin on oviposition is regulated by the juvenile hormone (JH) signaling pathway in C. pomonella, allowing it to prioritize survival. The enhanced reproductive fitness of G. molesta in response to quercetin is attributed to the regulation of JH titers and key genes such as Met and Kr-h1, which in turn up-regulate reproduction-related genes Vg and VgR. In contrast, C. pomonella is inhibited. These findings shed light on the mechanisms interspecific competition and help to improve our understanding of the global spread of C. pomonella, which can be attributed to its inherent superiority in terms of reproductive strategy.
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Mariposas Nocturnas , Animales , Femenino , Quercetina/farmacología , Hormonas Juveniles/farmacología , Oviposición , Frutas , Transducción de SeñalRESUMEN
Background: The prevalence of eosinophilic chronic rhinosinusitis (ECRS) has increased in Taiwan with a higher recurrence rate of nasal polyps after surgery. Therefore, we aimed to formulate the pre-operative diagnostic criteria for patients with ECRS in Taiwan. Methods: This case-control study included patients diagnosed with CRS with nasal polyps (CRSwNP) who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. The patients were classified into ECRS and non-eosinophilic CRS (NECRS) groups based on their histopathology. Demographic data, symptom severity scores, and computed tomography findings of the two groups were analyzed. We utilized receiver operating characteristic curve (ROC) analysis to evaluate parameters that could predict the diagnosis of ECRS. Results: Total 408 CRSwNP patients were enrolled (ECRS group: 163; NECRS group: 245). ECRS group was strongly associated with asthma (6.1% vs. 2.0%, p = .03), higher blood eosinophil counts (4.3% vs. 2.7%, p < .01), higher serum IgE (285.3 vs. 50.2 IU/mL, p = .02), and higher 22-item Sino-Nasal Outcome Test (SNOT-22) score (40.5 vs. 36.7, p = .03). The ECRS criteria based on ROC curve included the SNOT-22 (>45, 2 points), serum eosinophil count percentage (>4%, 4 points), asthma (4 points), total serum IgE (>140 IU/mL, 4 points), Lund-Mackay score (>9.5, 4 points), and ethmoid-to-maxillary opacification ratio on CT (>1.5, 5 points). The cutoff score was 14 points (sensitivity, 70.2%; specificity, 93.3%). Conclusions: Clinical-feature-based criteria may predict the diagnosis of ECRS before FESS in Taiwan. Level of Evidence: Level 3.
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A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.
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Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Humanos , Masculino , Persona de Mediana Edad , Adulto , Femenino , Estudios de Cohortes , Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Súbita/diagnóstico por imagen , Pérdida Auditiva Súbita/complicaciones , Pérdida Auditiva Súbita/terapia , Audición , Neuroimagen , Estudios RetrospectivosRESUMEN
BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.