Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study.

Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice.

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Cognition, attitude, practice toward health checkup and associated factors among urban residents in southwest China, Sichuan province, 2022: a community-based study.

Aim: Research on the health checkup status of urban residents in Southwest China is limited. In this study, we aimed to investigate the current status of health checkups and explore their influencing factors by analyzing the cognition, attitudes, and practices of urban residents in Southwest China. Methods: We sampled 1200 urban residents for a questionnaire survey. Statistical analysis was performed using SPSS 23, and logistic regression analysis was used to analyze the factors affecting cognition, attitudes, and practices regarding health checkups. A P value < 0.05 was used to identify variables significantly associated with the outcome variable. Results: Overall, 29% of the residents understood the importance of health checkups. The main ways urban residents acquire health-related knowledge are through the use of mobile media and medical staff health education. Only 40% of residents had undergone a regular checkup. Health self-assessment, economic reasons, and time are the factors that interfere with urban residents' health checkups. Logistic regression analysis showed that occupation status, educational background, self-assessed health status, exercise status, and monthly income level were the common influencing factors of health checkup cognition and planning. Whether residents had participated in a medical checkup program was also related to sex and age. Conclusions: Urban residents in Southwest China generally had a high willingness to undergo physical examinations, but there were differences in knowledge and practice; at the same time, residents lacked understanding of respiratory assessments. Improving the health literacy of medical staff, strengthening urban residents' health education, and enhancing the utilization rate of health checkups in urban residents are necessary and urgent.

Positioning Error Analysis and Control of a Piezo-Driven 6-DOF Micro-Positioner.

This paper presents a positioning error model and a control compensation scheme for a six-degree-of-freedom (6-DOF) micro-positioner based on a compliant mechanism and piezoelectric actuators (PZT). The positioning error model is established by means of the kinematic model of the compliant mechanism and complete differential coefficient theory, which includes the relationships between three typical errors (hysteresis, machining and measuring errors) and the total positioning error. The quantitative analysis of three errors is demonstrated through several experimental studies. Afterwards, an inverse Presiach model-based feedforward compensation of the hysteresis nonlinearity is employed by the control scheme, combined with a proportional-integral-derivative (PID) feedback controller for the compensation of machining and measuring errors. Moreover, a back propagation neural network PID (BP-PID) controller and a cerebellar model articulation controller neural network PID (CMAC-PID) controller are also adopted and compared to obtain optimal control. Taking the translational motion along the X axis as an example, the positioning errors are sharply reduced by the inverse hysteresis model with the maximum error of 12.76% and a root-mean-square error of 4.09%. In combination with the CMAC-PID controller, the errors are decreased to 0.63% and 0.23%, respectively. Hence, simulated and experimental results reveal that the proposed approach can improve the positioning accuracy of 6-DOF for the micro-positioner.

Modelling and Analysis of Characteristics of a Piezoelectric-Actuated Micro-/Nano Compliant Platform Using Bond Graph Approach.

The piezoelectric-actuated flexure-based compliant platform is commonly adopted in many fields of micro and nanotechnology. In this paper, bond graph modeling, and kinematic and dynamic characteristics of a piezoelectric-actuated micro-/nano compliant platform system are investigated. During modeling, the bond graph model of the piezoelectric actuator (PZT) is derived by considering both the electrical domain and the mechanical domain. Considering the compliances of flexure hinges and elastic linkages, as well as the input ends, the bond graph model for the bridge-type displacement amplification mechanism in the compliant platform is established by combining pseudo-rigid-body (PRB) model theory and elastic beam theory. Based on the interactions between the PZT subsystem and compliant platform subsystem, the kinematic performance of the proposed compliant platform system is evaluated through both computer simulations and experimental tests. Furthermore, the frequency responses, dynamic responses and load capacity of the compliant platform system are studied. This paper explores a new modeling method for a piezoelectric-actuated compliant platform system, which can provide an effective solution when analyzing the micro-/nano system.

The role and gene expression profile of SOCS3 in colorectal carcinoma.

SOCS3 has been postulated to play a role in the occurrence and progression of malignancies. However, the relationship of SOCS3 with colorectal carcinoma remains poorly understood. The purpose of the study was to explore the role of SOCS3 in colorectal carcinoma and its underlying mechanisms. Protein and mRNA expression of SOCS3 in colorectal carcinoma and normal colorectal mucosa was detected using immunohistochemistry and real-time quantitative PCR. SOCS3 expression was significantly lower in colorectal carcinoma tissue than in normal colorectal mucosa, and was negatively correlated with tumor invasion depth, lymph node metastasis, differentiation degree, and TNM stage. A stably transfected colorectal carcinoma cell line (8348SOCS3) with high expression of SOCS3 was established. The effects of SOCS3 overexpression on the growth, proliferation, invasion and tumor formation of colorectal carcinoma cells were examined by CCK-8 assay, transwell method and tumorigenicity assays in nude mice. Then we found SOCS3 overexpression significantly decreased proliferation and invasion capability of 8348 cells in vitro and in vivo. Furthermore, the effect of SOCS3 overexpression on the gene expression profile of colorectal carcinoma cells was analyzed using human genome arrays. The results revealed 369 genes that were differentially expressed in 8348SOCS3 cells. 193 genes was significantly increased and 176 genes was significantly decreased. Bioinformatics analysis demonstrated that high SOCS3 expression affected multiple signaling pathways in colorectal carcinoma including TGF-ß/Smads, NF-κB, and HIF-MAPK pathways. Especially for the TGF-ß/Smads pathways, high SOCS3 expression could inhibit TGF-ß1 expression and activate Smad4 expression. These data suggested that low expression of SOCS3 was associated with the occurrence and progression of colorectal carcinoma. SOCS3 protein may be a useful indicator for malignancy and prognosis of colorectal carcinoma and also a new target for gene therapy.

Inhibition of P38 MAPK Downregulates the Expression of IL-1ß to Protect Lung from Acute Injury in Intestinal Ischemia Reperfusion Rats.

Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1ß was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1ß to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1ß and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1ß and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and ß, could effectively downregulate the expressions of IL-1ß and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and ß may downregulate the expression of IL-1ß to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.

Historical levels of heavy metals reconstructed from sedimentary record in the Hejiang River, located in a typical mining region of Southern China.

Historical levels of Pb, Zn, Cd, Cr, Cu, Ni, As, Fe, Al and Mn were found in C1 and C2 sediment cores from the Hejiang River, which is located in a typical mining region of Southern China, the levels date back approximately 57 and 83 years. Temporal variations in the core C1 around the mining peaked in the 1960s, after which they exhibited a decreasing trend, which reflects successful government management. Historical events such as the Pacific War and China's first 5-year economic plan were recorded in core C2, which was collected from the downstream portion of the Hejiang River. Enrichment factors (EF), geo-accumulation (Igeo), and excess flux indicate that severe contamination occurred during the period between 1956 and 1985 due to the release of high amounts of mining waste from human activities around the core C1 region. The highest EF value was displayed by As (67); this was followed by Pb (64), Cd (39), and Zn (35). In contrast, the core C2 sediments exhibited minor pollution because of dilution from tributaries (the Fu River and the Daning River) that do not flow through the mined area and because C2 was farther from the source of the metals. The results of the risk assessment codes (RAC) for both cores indicate that Cd posed a high risk to the local environment. Principal component analysis (PCA) and correlation analysis (CA) revealed that accumulation of heavy metals was mainly due to mining pollution.

Influence of anthropogenic activities on PAHs in sediments in a significant gulf of low-latitude developing regions, the Beibu Gulf, South China Sea: distribution, sources, inventory and probability risk.

Fifteen polycyclic aromatic hydrocarbons (PAHs) in 41 surface sediment samples and a sediment core (50 cm) from the Beibu Gulf, a significant low-latitude developing gulf, were analyzed. PAHs concentrations were 3.01-388 ng g(-)(1) (mean 95.5 ng g(-)(1)) in the surface sediments and 10.5-87.1 ng g(-)(1) (average 41.1 ng g(-)(1)) in the sediment core. Source apportionment indicated that PAHs were generated from coke production and vehicular emissions (39.4%), coal and biomass combustion (35.8%), and petrogenic sources (24.8%). PAHs were mainly concentrated in the industrialized and urbanized regions and the harbor, and were transported by atmospheric deposition to the marine matrix. The mass inventory (1.57-2.62t) and probability risk showed sediments here served as an important reservoir but low PAH risk. Different from oil and natural gas in developed regions, coal combustion has always been a significant energy consumption pattern in this developing region for the past 30 years (56 ± 5%).

Occurrence, distribution and sources of organochlorine pesticides (OCPs) in surface sediments from the Lijiang River, a typical karst river of southwestern China.

The Lijiang River is a typical karst river of southwestern China. Karst-aquifer systems are more vulnerable to contamination compared to other types of aquifers. The occurrence and distribution of organochlorine pesticides (OCPs) in surface sediments from the Lijiang River were investigated to evaluate their potential ecological risks. The total concentrations of them in sediments ranged from 0.80 to 18.73 ng/g dry weight (dw) (mean 6.83 ng/g dw). The residue levels of OCPs varied in the order of HCB > HCHs > DDTs. Compositional analyses of OCPs showed that HCHs and DDTs were mainly from historical usage. The ecological risk assessment suggested that HCHs and DDTs in Lijiang River sediments may cause adverse ecological risks, particularly at sites near agricultural areas.

Sixty-year sedimentary record of DDTs, HCHs, CHLs and endosulfan from emerging development gulfs: a case study in the Beibu Gulf, South China Sea.

The temporal distribution of organochlorine pesticides (OCPs) was examined in the (210)Pb dated sediment core from the Beibu Gulf, South China Sea. The total OCPs concentrations were in the range of 0.93-26.6 ng g(-1) dry weight. Dichlorodiphenyltrichloroethanes (DDTs) (0.17-24.8 ng g(-1)), Hexachlorocyclohexanes (HCHs) (0.04-0.51 ng g(-1)), Chlordane related compounds (CHLs) (0.22-1.72 ng g(-1)) and endosulfan (n.d.-0.91 ng g(-1)) were the predominant compounds. Similar to most Chinese coastal areas, the levels of DDTs in the Beibu Gulf became elevated since the early 1990s, especially since 2000 despite the ban in 1983 in China. This suggests that the concentrations of DDTs were controlled by several processes, such as land reclamation and soil runoff. The isomer ratios of (p,p'-DDE + p,p'-DDD)/p,p'-DDT, p,p'-DDT/DDTs along with construction land expansion indicated that economic activities, land reclamation, soil runoff and the use of DDT-containing antifouling paints might be responsible for the input of DDT. The ratios of α-HCH/γ-HCH (and γ-HCH/HCHs) and trans-chlordane/cis-chlordane (TC/CC) indicated fresh inputs of lindane and chlordane, respectively. In addition, CC was found to be degraded faster than TC under anaerobic conditions in sediments from the Beibu Gulf.

Facilitation of the inhibitory transmission by gastrin-releasing peptide in the anterior cingulate cortex.

Gastrin-releasing peptide (GRP) has been proposed as a peptidergic molecule for behavioral fear and itching. Immunohistochemistry and in situ hybridization studies have shown that GRP and GRP receptor are widely distributed in forebrain areas. Less information is available for the functional action for GRP in the prefrontal cortex including the anterior cingulate cortex (ACC). Here we used whole-cell patch-clamp recording technique to study the modulation of synaptic transmission by GRP in the ACC. We found that GRP increased the frequency of sIPSCs recorded while had no significant effect on sEPSCs in ACC pyramidal neurons. The facilitatory effect of GRP on sIPSCs was blocked by the GRP receptor antagonist, RC3095. In the presence of TTX, however, GRP had no effect on the mIPSCs. Therefore, activation of GRP receptor may facilitate the excitation of the interneurons and enhanced spontaneous GABAergic, but not glutamatergic neurotransmission. Similar results on GRP modulation of GABAergic transmission were observed in the insular cortex and amygdala, suggesting a general possible effect of GRP on cortical inhibitory transmission. Our results suggest that GRP receptor is an important regulator of inhibitory circuits in forebrain areas.

Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development.

Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency-intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation-inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.

Intervening inhibition underlies simple-cell receptive field structure in visual cortex.

Synaptic inputs underlying spike receptive fields are important for understanding mechanisms of neuronal processing. Using whole-cell voltage-clamp recordings from neurons in mouse primary visual cortex, we examined the spatial patterns of their excitatory and inhibitory synaptic inputs evoked by On and Off stimuli. Neurons with either segregated or overlapped On/Off spike subfields had substantial overlaps between all the four synaptic subfields. The segregated receptive-field structures were generated by the integration of excitation and inhibition with a stereotypic 'overlap-but-mismatched' pattern: the peaks of excitatory On/Off subfields were separated and flanked colocalized peaks of inhibitory On/Off subfields. The small mismatch of excitation/inhibition led to an asymmetric inhibitory shaping of On/Off spatial tunings, resulting in a great enhancement of their distinctiveness. Thus, slightly separated On/Off excitation, together with intervening inhibition, can create simple-cell receptive-field structure and the dichotomy of receptive-field structures may arise from a fine-tuning of the spatial arrangement of synaptic inputs.

Visual receptive field structure of cortical inhibitory neurons revealed by two-photon imaging guided recording.

Synaptic inhibition plays an important role in shaping receptive field (RF) properties in the visual cortex. However, the underlying mechanisms remain not well understood, partly because of difficulties in systematically studying functional properties of cortical inhibitory neurons in vivo. Here, we established two-photon imaging guided cell-attached recordings from genetically labeled inhibitory neurons and nearby "shadowed" excitatory neurons in the primary visual cortex of adult mice. Our results revealed that in layer 2/3, the majority of excitatory neurons exhibited both On and Off spike subfields, with their spatial arrangement varying from being completely segregated to overlapped. In contrast, most layer 4 excitatory neurons exhibited only one discernable subfield. Interestingly, no RF structure with significantly segregated On and Off subfields was observed for layer 2/3 inhibitory neurons of either the fast-spike or regular-spike type. They predominantly possessed overlapped On and Off subfields with a significantly larger size than the excitatory neurons and exhibited much weaker orientation tuning. These results from the mouse visual cortex suggest that different from the push-pull model proposed for simple cells, layer 2/3 simple-type neurons with segregated spike On and Off subfields likely receive spatially overlapped inhibitory On and Off inputs. We propose that the phase-insensitive inhibition can enhance the spatial distinctiveness of On and Off subfields through a gain control mechanism.

Nonmonotonic synaptic excitation and imbalanced inhibition underlying cortical intensity tuning.

Intensity-tuned neurons, characterized by their nonmonotonic response-level function, may play important roles in the encoding of sound intensity-related information. The synaptic mechanisms underlying intensity tuning remain unclear. Here, in vivo whole-cell recordings in rat auditory cortex revealed that intensity-tuned neurons, mostly clustered in a posterior zone, receive imbalanced tone-evoked excitatory and inhibitory synaptic inputs. Excitatory inputs exhibit nonmonotonic intensity tuning, whereas with tone intensity increments, the temporally delayed inhibitory inputs increase monotonically in strength. In addition, this delay reduces with the increase of intensity, resulting in an enhanced suppression of excitation at high intensities and a significant sharpening of intensity tuning. In contrast, non-intensity-tuned neurons exhibit covaried excitatory and inhibitory inputs, and the relative time interval between them is stable with intensity increments, resulting in monotonic response-level function. Thus, cortical intensity tuning is primarily determined by excitatory inputs and shaped by cortical inhibition through a dynamic control of excitatory and inhibitory timing.