Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels.

Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, S1R has become a novel target for antidepression therapy. With a rapid and sustained antidepressant effect, ketamine may also interact with S1R. In this study, we investigated whether the antidepressant action of ketamine was related to S1R activation. Depression state was evaluated in the tail suspension test (TST) and a chronic corticosterone (CORT) procedure was used to induce despair-like behavior in mice. The neuronal activities and structural changes of pyramidal neurons in medial prefrontal cortex (mPFC) were assessed using fiber-optic recording and immunofluorescence staining, respectively. We showed that pharmacological manipulation of S1R modulated ketamine-induced behavioral effect. Furthermore, pretreatment with an S1R antagonist BD1047 (3 mg·kg-1·d-1, i.p., for 3 consecutive days) significantly weakened the structural and functional restoration of pyramidal neuron in mPFC caused by ketamine (10 mg·kg-1, i.p., once). Ketamine indirectly triggered the activation of S1R and subsequently increased the level of BDNF. Pretreatment with an S1R agonist SA4503 (1 mg·kg-1·d-1, i.p., for 3 consecutive days) enhanced the sustained antidepressant effect of ketamine, which was eliminated by knockdown of BDNF in mPFC. These results reveal a critical role of S1R in the sustained antidepressant effect of ketamine, and suggest that a combination of ketamine and S1R agonists may be more beneficial for depression patients.

Application Effect of Patient-centered Health Education in Patients with Type 2 Diabetes Accompanied by Hyperlipidemia.

Objective: This study aims to investigate the impact of patient-centered health education on individuals with type 2 diabetes coexisting with hyperlipidemia. Methods: A cohort of 80 patients with type 2 diabetes and hyperlipidemia attending our hospital from February 2022 to August 2022 were randomly assigned to either the health education group or the control group. While the control group received routine health education, the health education group received additional patient-centered health education. Subsequently, we compared blood glucose and lipid levels, negative emotions, quality of life, and the incidence of unhealthy eating or overweight between the two groups post-education. Results: Following the health education intervention, the health education group exhibited superior improvements in blood glucose and lipid levels compared to the control group. Moreover, there was a significant decrease in SAS and SDS scores and a notable increase in quality of life compared to the control group. The health education group also demonstrated a lower incidence of unhealthy eating or overweight. Conclusions: Patient-centered health education for individuals with type 2 diabetes and hyperlipidemia proves effective in enhancing glucose and lipid metabolism, mitigating negative emotions, improving quality of life, and reducing unhealthy habits.

Health risks from extreme heat in China: Evidence from health insurance.

Global warming has accentuated the effects of extreme heat on health. Health insurance, functioning as a risk management tool, has the potential to alleviate these impacts. Consequently, this paper investigates the correlation between extreme heat events and the demand for health insurance in China. Using data from the China Health and Nutrition Survey, we have observed a substantial increase in the likelihood of residents purchasing health insurance during extreme heat events. To be specific, for every extra day of extreme heat events annually, there is a 0.3% increase in the probability of purchasing health insurance. This effect is not uniform across different demographic groups. It is particularly pronounced among middle-aged and elderly individuals, rural residents, those with lower educational levels, higher income brackets, and individuals residing in underprivileged areas with limited access to green spaces and healthcare facilities. Furthermore, our study indicates that the increased frequency of extreme heat events not only impacts individuals' physical health but also triggers negative emotions, which in turn drive risk-averse behavior related to health insurance purchases. These findings carry substantial policy implications for mitigating the economic consequences of climate change.

Effects of motivational interviewing intervention on psychological status, compliance behavior and quality of life of patients with malignant tumor combined with diabetes mellitus.

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.

Targeted blocking of CCR2 and CXCR2 improves the efficacy of transarterial chemoembolization of hepatocarcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) has been shown to prolong survival in patients with unresectable hepatocellular carcinoma (HCC); however, the long-term survival remains dismal. Targeting macrophage and neutrophil infiltration is a promising strategy. The CCL2/CCR2 and CXCLs/CXCR2 axes are required for recruitment of macrophages and neutrophils, respectively, in HCC. We investigated the feasibility of CCL2/CCR2 and CXCLs/CXCR2 as therapeutic targets in combination with TACE for treating HCC. METHODS: Expression of CCL2/CCR2 and CXCLs/CXCR2 was analyzed in the primary rat HCC model and one HCC cohort. The relationship between expression levels, neutrophil and macrophage infiltration, hepatocarcinogenesis progression in the rat model, and survival of HCC patients was assessed. The anti-tumor effects of blocking the CCL2/CCR2 and CXCLs/CXCR2 axes by CCR2 and CXCR2 antagonists in combination with TACE were evaluated in HCC rats. The numbers of macrophages, neutrophils, and hepatic progenitor cells were further determined to explore the underlying mechanisms. RESULTS: High macrophage and neutrophil infiltration and CXCL8 expression were associated with poor prognosis in the TCGA liver cancer dataset. High expression of CCL2/CCR2 and CXCL8/CXCR2 in clinical HCC specimens was associated with reduced survival. Expression of CCL2/CCR2 and CXCL1/CXCR2 was correlated with hepatocarcinogenesis progression in the primary rat HCC model. Blockade of CCL2/CCR2 and CXCLs/CXCR2 enhanced the anti-tumor effect of TACE treatment in this model. Blocking the CCL2/CCR2 and CXCLs/CXCR2 axes with CCR2 and CXCR2 antagonists in TACE-treated rats reduced macrophage and neutrophil infiltration and hepatic progenitor cell activation and thus overcame TACE resistance in HCC. CONCLUSIONS: The results demonstrate the translational potential of immunotherapy targeting the CCL2/CCR2 and CXCLs/CXCR2 axes in combination with TACE therapy for the treatment of HCC.

Extracellular microparticles derived from hepatic progenitor cells deliver a death signal to hepatoma-initiating cells.

The malignant transformation of normal resident hepatic stem/progenitor cells has a critical role in hepatocarcinogenesis and the recurrence of hepatocellular carcinoma (HCC). We defined such hepatic progenitor cells as hepatoma-initiating cells. An efficient strategy is required to target and kill the hepatoma-initiating cells. We isolated extracellular microparticles (MPs) derived from apoptotic hepatic progenitor cells (HPCs) and tested their ability to inhibit hepatocarcinogenesis. Extracellular MPs were isolated from HPCs, hepatocytes and liver tumor cells. Their effects on tumor growth were investigated in rat primary HCC models, in which hepatocarcinogenesis is induced by diethylnitrosamine (DEN). The extracellular MPs derived from apoptotic HPCs, apoptotic hepatocytes and apoptotic liver tumor cells were similar in morphology, diameter and zeta potential. However, they had different antitumor effects. In DEN-exposed rats, only the MPs derived from apoptotic HPCs effectively inhibit hepatocarcinogenesis. In vitro and in vivo analyses confirmed that HPCs preferentially take up MPs derived from apoptotic HPCs compared to MPs from other liver cell types. Proteomic analysis of MPs from apoptotic HPCs showed enrichment of proteins involved in cell death pathways. Thus, HPC-derived MPs contain a death signal to induce the killing of hepatoma-initiating cells. Our findings provide evidence that a death signal encapsulated in HPC-derived extracellular microparticles can efficiently clear hepatoma-initiating cells and prevent hepatocarcinogenesis.

Phytochemical and comparative transcriptome analyses reveal different regulatory mechanisms in the terpenoid biosynthesis pathways between Matricaria recutita L. and Chamaemelum nobile L.

BACKGROUND: Matricaria recutita (German chamomile) and Chamaemelum nobile (Roman chamomile) belong to the botanical family Asteraceae. These two herbs are not only morphologically distinguishable, but their secondary metabolites - especially the essential oils present in flowers are also different, especially the terpenoids. The aim of this project was to preliminarily identify regulatory mechanisms in the terpenoid biosynthetic pathways that differ between German and Roman chamomile by performing comparative transcriptomic and metabolomic analyses. RESULTS: We determined the content of essential oils in disk florets and ray florets in these two chamomile species, and found that the terpenoid content in flowers of German chamomile is greater than that of Roman chamomile. In addition, a comparative RNA-seq analysis of German and Roman chamomile showed that 54% of genes shared > 75% sequence identity between the two species. In particular, more highly expressed DEGs (differentially expressed genes) and TF (transcription factor) genes, different regulation of CYPs (cytochrome P450 enzymes), and rapid evolution of downstream genes in the terpenoid biosynthetic pathway of German chamomile could be the main reasons to explain the differences in the types and levels of terpenoid compounds in these two species. In addition, a phylogenetic tree constructed from single copy genes showed that German chamomile and Roman chamomile are closely related to Chrysanthemum nankingense. CONCLUSION: This work provides the first insights into terpenoid biosynthesis in two species of chamomile. The candidate unigenes related to terpenoid biosynthesis will be important in molecular breeding approaches to modulate the essential oil composition of Matricaria recutita and Chamaemelum nobile.

A high-resolution flexible sensor array based on PZT nanofibers.

Flexible tactile sensor array has drawn great attention due to its ability to mimic human skin for sensing weak pressure and distinguishing pressure distribution, but the deficiency of sensitivity, the low resolution, and the complex and costly fabrication process seriously limit its development. Hence, it is urgent to explore a fully flexible sensor array with high sensitivity and high resolution as an electronic-skin. Here, the flexible piezoelectric tactile sensor array based on the composite film of PZT nanowires and polydimethylsiloxane (PDMS) was fabricated by the simple fabrication process (electrospinning process and mixture process). The electrospun PZT nanofibers have high aspect ratio and could enhance the generation and accumulation of the piezoelectric charges in the two electrodes of the composite film. By virtue of the inherently high piezoelectric coefficient of PZT material and high aspect ratio of PZT nanofibers, the composite film (75 wt% PZT nanofibers) presents high force-electric conversion capability and high sensitivity. Owing to the bottom electrode sheet shared by all sensor units and the supporting layer with relatively high elastic modulus, the sensor array shows high resolution to qualitatively sense the distribution and size of the impact in real time. Moreover, the sensor array also shows great durability, repeatability, and large working range. Based on these excellent characteristics, the sensor array has wide potential applications in the field of bionics science, robotics science and human-machine interaction.

Autophagy and Tumour Chemotherapy.

Chemotherapy is an important means of treating malignant tumours. The main role of chemotherapy drugs is to induce cell death. However, the apoptotic pathways of many tumour cells are often severely impaired, leading to failure of chemotherapy-induced apoptosis. With the in-depth study of autophagy in recent years, this process has been found to play an important role in the chemoresistance of tumours. Autophagy may have different effects on tumour cells depending on the specific environment. In addition, tumour stem cells and the tumour microenvironment are closely related to tumour recurrence and metastasis. It is also important to study the role of autophagy in tumour stem cells and the microenvironment to investigate chemotherapy resistance.

Lipopolysaccharide protects against acetaminophen-induced hepatotoxicity by reducing oxidative stress via the TNF-α/TNFR1 pathway.

Robust evidence suggested that gut-derived lipopolysaccharide (LPS) plays a significant role in various liver injury diseases; however, the role of gut-derived LPS in acetaminophen (APAP) overdose-induced acute liver injury remains unclear. The present study aimed to investigate the effect of gut-derived LPS on APAP-induced liver injury. Our results revealed that reduction of gut-derived LPS using multiple antibiotics could significantly exacerbate APAP-induced liver injury and increase mortality in mice. By contrast, pretreatment with exogenous LPS could reverse APAP-induced liver hepatotoxicity in mice and rats. We observed that TNF-α secretion in the liver was significantly increased after LPS pretreatment. In addition, depletion of TNF-α or TNFR1 inhibited the protective effects of LPS against APAP-induced hepatotoxicity, which indicated that the TNF-α/TNFR1 pathway was required to protect against APAP-induced liver injury. Mechanistically, LPS reduces oxidative stress by upregulating the expression of hepatic GSH, reducing MDA levels in liver tissues, and upregulating the expression of several antioxidant genes after APAP injection. However, the production of hepatic GSH was not enhanced in the liver tissues of rats lacking TNF-α or TNFR1 and MDA levels were not reduced after LPS and APAP co-treatment. The above results suggested LPS alleviated APAP-induced oxidative stress via the TNF-α/TNFR1 pathway.

Thickness Dependence of Ferroelectric and Optical Properties in Pb(Zr0.53Ti0.47)O3 Thin Films.

As a promising functional material, ferroelectric Pb(ZrxTi1-x)O3 (PZT) are widely used in many optical and electronic devices. Remarkably, as the film thickness decreases, the materials' properties deviate gradually from those of solid materials. In this work, multilayered PZT thin films with different thicknesses are fabricated by Sol-Gel technique. The thickness effect on its microstructure, ferroelectric, and optical properties has been studied. It is found that the surface quality and the crystalline structure vary with the film thickness. Moreover, the increasing film thickness results in a significant increase in remnant polarization, due to the interfacial layer effect. Meanwhile, the dielectric loss and tunability are strongly dependent on thickness. In terms of optical properties, the refractive index of PZT films increase with the increasing thickness, and the photorefractive effect are also influenced by the thickness, which could all be related to the film density and photovoltaic effect. Besides, the band gap decreases as the film thickness increases. This work is significant for the application of PZT thin film in optical and optoelectronic devices.

Immune response involved in liver damage and the activation of hepatic progenitor cells during liver tumorigenesis.

Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well-known leading causes of HCC. However, the mechanism of the induction of HCC by these virus is still being debated. This review will focus on the current knowledge of the pathogenesis of HBV- and HCV-induced inflammation and the role of such immune activation in the tumorigenesis of HCC. It is well established that the recruitment of certain number and type of immune cells to liver is essential for the resolution of HBV and HCV infection and the prevention of subsequent chronic persistent infection. However, in case that the immune response do not completely clear virus, persistent chronic infection occurs, and the perpetual immune response may contribute to chronic damages of the liver. Such chronic inflammatory damages further harm hepatocytes, but not hepatic progenitor cells (HPCs). Thus, following chronic damages, HPCs are activated and their dysregulated proliferation ensures survival in the hostile environment, contributing to the tumorigenesis of HCC. Furthermore, accumulating evidence also provides a strong link between HPCs and human hepatocellular carcinoma. Collectively, these findings support a notion that immune response is involved in liver damage during hepatitis virus infection, and the activation and dysregulated differentiation of hepatic progenitor cells promote the tumorigenesis of human hepatocellular carcinoma.

Tunable artificial microwave blackbodies based on metasurfaces.

Inspired by the classic hole-cavity blackbody model, we propose an open metasurface blackbody operating at microwave frequencies, whose unit cell is a dielectric resonator lying on an opaque metal plate. The resonator has a high temperature coefficient of dielectric constant, thus the blackbody can be thermally tunable. Furthermore, when the resonator is combined with ferrite, a magnetically tunable blackbody is also obtained. Absorption spectra of these two tunable blackbody unit cells are measured, and they agree very well with the simulated results. The proposed blackbodies offer a new opportunity for practical tunable microwave absorbers in applications.

Has the medical reform improved the cost efficiency of Chinese hospitals?

After three decades of reform, the medical care system in China has experienced significant changes. However, the present research has not made a tentative evaluation of it to justify further reform. This paper analyses the cost efficiency of Chinese hospitals in 31 provinces during the period from 2002 to 2011 and adopts a Bayesian stochastic frontier model taking account of the identified heterogeneity according to the background of Chinese medical system reform, including the coastal location, 3A class hospital proportion, public subsidies and medical insurance reforms. It finds that the public subsidies and medical insurance reforms have improved the cost efficiency of Chinese hospitals, while the coastal location and 3A class hospital proportion have decreased the cost efficiency of Chinese hospitals. Therefore, these results imply that it will be beneficial for Chinese medical system to optimize the fiscal subsidies of public hospitals, encourage the entrance of private hospitals, improve the medical insurance coverage and set up the pre-triage system.

Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells.

A series of novel chiral ruthenium(II) polypyridyl complexes (Δ-Ru1, Λ-Ru1, Δ-Ru2, Λ-Ru2, Δ-Ru3, Λ-Ru3) were synthesized and evaluated to determine their antiproliferative activities. Colocalization, inductively coupled plasma mass spectrometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay studies showed that these ruthenium(II) complexes accumulated preferentially in the mitochondria and exhibited cytotoxicity against various cancer cells in vitro. The complex Δ-Ru1 is of particular interest because it was found to have half-maximal inhibitory concentrations comparable to those of cisplatin and better activity than cisplatin against a cisplatin-resistant cell line, A549-CP/R. Δ-Ru1 induced alterations in the mitochondrial membrane potential and triggered intrinsic mitochondria-mediated apoptosis in HeLa cells, which involved the regulation of Bcl-2 family members and the activation of caspases. Taken together, these data suggest that Δ-Ru1 may be a novel mitochondria-targeting anticancer agent.

A modified heterotopic auxiliary living donor liver transplantation: report of a case.

Liver transplantation is regarded as an effective treatment for Wilson's disease (WD), and recently has been shown to improve not only hepatic but also neurologic manifestations. Conventional auxiliary liver transplantation for WD is orthotopic liver transplantation and heterotopic liver transplantation. But the conventional procedure could not avoid the problem of space, functional competition, hemodynamic variation. Here we report a case of heterotopic auxiliary living-donor liver transplantation (HALDLT) to treat WD. We modified the operation to have a splenectomy, implant graft into the splenic fossa. The patient recovered well after the transplantation and has been symptom-free during a 5-year follow-up. This modified operation is more safe and simple. HALDLT might be an effective treatment for WD patients with splenomegaly.

Adaptation of the egg of the desert beetle, Microdera punctipennis (Coleoptera: Tenebrionidae), to arid environment.

Microdera punctipennis Kaszab (Coleoptera: Tenebrionidae) is an endemic species in Guerbantonggut desert in China. To explore the ways that M. punctipennis egg adapts to dry desert environment, morphological characteristics of the egg was investigated along with the egg of the nondesert beetle Tenebrio molitor (Coleoptera: Tenebrionidae). Water loss rate and survival rate of these eggs under different dry treatments (relative humidity0, 10, and 20%) were measured to evaluate the desiccation resistance of the eggs at different developmental stages (day 0, 2, and 5 eggs). Our results showed that the 50-egg weight in T. molitor was heavier than M. punctipennis, while the 50-first-instar larva weight in T. molitor was almost the same as in M. punctipennis. The water loss rate of M. punctipennis egg under dry conditions was significantly lower than T. molitor, and the egg survival rate was significantly higher than T. molitor. The estimated developmental threshold temperature of M. punctipennis egg was 18.30°C, and the critical thermal maximum of M. punctipennis egg is above 39°C. These features partly account for the adaptability of M. punctipennis to desert environment in egg stage.

Fiber-based flexible all-solid-state asymmetric supercapacitors for integrated photodetecting system.

Integrated nanodevices with the capability of storing energy are widely applicable and have thus been studied extensively. To meet the demand for flexible integrated devices, all-solid-state asymmetric supercapacitors that simultaneously realize energy storage and optoelectronic detection were fabricated by growing Co3 O4 nanowires on nickel fibers, thus giving the positive electrode, and employing graphene as both the negative electrode and light-sensitive material. The as-assembled integrated systems were characterized by an improved energy storage, enhanced power density (at least by 1860 % enhanced) by improving the potential window from 0-0.6 V to 0-1.5 V, excellent photoresponse to white light, and superior flexibility of both the fiber-based asymmetric supercapacitor and the photodetector. Such flexible integrated devices might be used in smart and self-powered sensory, wearable, and portable electronics.

Extreme high temperatures and corporate low-carbon actions.

Greenhouse gas emissions are considered the culprit of extreme high temperatures, and low-carbon transformation has become a global consensus. The low-carbon action by enterprises is an inevitable choice if they are to adapt to economic and social needs. Green innovation is an important measure for enterprises to respond to the challenges of low-carbon transformation. This study mainly discusses the causal relationship between extreme high temperatures and green innovation of enterprises. Using China's industrial enterprise database, we construct county-annual panel data from 2000 to 2013. Results show that extreme high temperatures improve the level of green innovation of enterprises. After a series of robustness tests, the results remain. Mechanism analysis shows that extreme high temperatures increase the environmental concerns of the government, the public, and society, thus strengthening government regulation, public participation, and social supervision as well as encouraging enterprises to carry out green innovation. Our heterogeneous analysis shows that in the eastern region with a high level of legal system and economic development, it is easier to promote green innovation for enterprises. In addition, large-scale enterprises are more willing to carry out green innovation after experiencing a heat wave.

Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment.

Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.