The impact of environmental regulation on green investment efficiency of thermal power enterprises in China-based on a three-stage exogenous variable model.

Due to the increased frequency of extreme weather events and the implementation of the China's dual-carbon target, thermal power companies have been under pressure to construct green infrastructure and to actively pursue low-carbon transformation in response to stricter environmental regulations. This research thus selects 30 listed thermal power enterprises in China as study objects and assesses their green investment efficiency in the low-carbon transition process using three-stage DEA evaluation model with environmental regulation as an exogenous variable. Based on this, a benchmark regression model is used to corroborate the relationship between environmental regulation and green investment. Simultaneously, we carry out analysis to compare the correlation between thermal power firms' green investment efficiency and their focus on green investments. The results show in terms of total efficiency that environmental regulation significantly improves the total efficiency of 80% of thermal power enterprises compared to the absence of this exogenous variable. With the addition of environmental regulation, firms' total efficiency declines gradually in general from 2018 to 2022, with the mean value of efficiency falling by 0.068. In terms of stage-specific efficiency, the efficiency of the green investment stage of the majority of firms is between 0.3 and 0.6, which is much lower than that of the operational stage and the market performance stage. In terms of sub-indicator efficiency, both green investment efficiency and social donation efficiency among thermal power enterprises show obvious polarization, with 30% of them having an efficiency of 1 and 30% less than 0.1. In terms of green investment focus, thermal power unit renovation has a more obvious role in boosting the green investment efficiency of thermal power enterprises than do wind power and photovoltaic projects. Therefore, both governmental departments and thermal power enterprises need to take active measures in order to achieve green transformation from the perspective of green investment efficiency. Through the segmentation of important projects of green investment, this paper provides a reasonable investment direction reference for the sustainable transformation of China's thermal power industry. It also provides a rich and novel theoretical basis for the Chinese government to further improve the relevant environmental protection laws and regulations of thermal power industry.

Size, distribution, and vulnerability of the global soil inorganic carbon.

Global estimates of the size, distribution, and vulnerability of soil inorganic carbon (SIC) remain largely unquantified. By compiling 223,593 field-based measurements and developing machine-learning models, we report that global soils store 2305 ± 636 (±1 SD) billion tonnes of carbon as SIC over the top 2-meter depth. Under future scenarios, soil acidification associated with nitrogen additions to terrestrial ecosystems will reduce global SIC (0.3 meters) up to 23 billion tonnes of carbon over the next 30 years, with India and China being the most affected. Our synthesis of present-day land-water carbon inventories and inland-water carbonate chemistry reveals that at least 1.13 ± 0.33 billion tonnes of inorganic carbon is lost to inland-waters through soils annually, resulting in large but overlooked impacts on atmospheric and hydrospheric carbon dynamics.

Ketogenic diet mitigates opioid-induced hyperalgesia by restoring short-chain fatty acids-producing bacteria in the gut.

ABSTRACT: Opioids are commonly prescribed to patients with chronic pain. Chronic opioid usage comes with a slew of serious side effects, including opioid-induced hyperalgesia (OIH). The patients with long-term opioid treatment experience paradoxical increases in nociceptive hypersensitivity, namely, OIH. Currently, treatment options for OIH are extremely lacking. In this study, we show that the ketogenic diet recovers the abnormal pain behavior caused by chronic morphine treatment in male mice, and we further show that the therapeutic effect of the ketogenic diet is mediated through gut microbiome. Our 16S rRNA sequencing demonstrates that chronic morphine treatment causes changes in mouse gut microbiota, specifically a decrease in short-chain fatty acids-producing bacteria, and the sequencing data also show that the ketogenic diet rescues those bacteria in the mouse gut. More importantly, we show that supplementation with short-chain fatty acids (butyrate, propionate, and acetate) can delay the onset of OIH, indicating that short-chain fatty acids play a direct role in the development of OIH. Our findings suggest that gut microbiome could be targeted to treat OIH, and the ketogenic diet can be used as a complementary approach for pain relief in patients with chronic opioid treatment. We only used male mice in this study, and thus, our findings cannot be generalized to both sexes.

Aggregation-induced signal amplification strategy based on peptide self-assembly for ultrasensitive electrochemical detection of melanoma biomarker.

The detection of melanoma circulating biomarker in liquid biopsies is current under evaluation for being potentially utilized for earlier cancer diagnosis and its metastasis. Herein, we developed a non-invasive electrochemical approach for ultrasensitive detection of the S100B, serving as a potential promising blood circulating biomarker of melanoma, based on an aggregation-induced signal amplification (AISA) strategy via in-situ peptide self-assembly. The fundamental principle of this assay is that the designed amphiphilic peptides (C16-Pep-Fc), fulfilling multiple functions, feature both a recognition region for specific binding to S100B and an aggregation (self-assembly) region for the formation of peptide nanomicelles under mild conditions. The C16 tails were encapsulated within the hydrophobic core of the aggregates, while the relatively hydrophilic recognition fragment Pep and Fc tag were exposed on the outer surface for subsequent recognition of S100B and signal output. AISA provided remarkable accumulation of electroactive Fc moieties that enabled ultrasensitive S100B detection of as low as 0.02 nM, which was 10-fold lower than un-amplified approach and better than previously reported assays. As a proof-of-concept study, further experiments also highlighted the good reproducibility and stability of AISA and demonstrated its usability when applied to simulated serum samples. Hence, this work not only presented a valuable assay tool for ultrasensitive detecting protein biomarker, but also advocated for the utilization of aggregation-induced signal amplification in electrochemical biosensing system, given its considerable potential for future practical applications.

TET1-mediated epigenetic regulation of tumor necrosis factor-α in trigeminal ganglia contributes to chronic temporomandibular joint pain.

Chronic temporomandibular joint (TMJ) pain profoundly affects patients' quality of life. Trigeminal tumor necrosis factor-α (TNFα) plays a pivotal role in mediating TMJ pain in mice, yet the underlying epigenetic mechanisms remain enigmatic. To unravel these epigenetic intricacies, we employed a multifaceted approach. Hydroxymethylated DNA immunoprecipitation (hMeDIP) and chromatin immunoprecipitation (ChIP) followed by qPCR were employed to investigate the demethylation of TNFα gene (Tnfa) and its regulation by ten-eleven translocation methylcytosine dioxygenase 1 (TET1) in a chronic TMJ pain mouse model. The global levels of 5-hydroxymethylcytosine (5hmc) and percentage of 5hmc at the Tnfa promoter region were measured in the trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) following complete Freund's adjuvant (CFA) or saline treatment. TET1 knockdown and pain behavioral testing were conducted to ascertain the role of TET1-mediated epigenetic regulation of TNFα in the pathogenesis of chronic TMJ pain. Our finding revealed an increase in 5hmc at the Tnfa promoter region in both TG and Sp5C of CFA-treated mice. TET1 was upregulated in the mouse TG, and the ChIP result showed TET1 direct binding to the Tnfa promoter, with higher efficiency in the CFA-treated group. Immunofluorescence revealed the predominant expression of TET1 in trigeminal neurons. TET1 knockdown in the TG significantly reversed CFA-induced TNFα upregulation and alleviated chronic TMJ pain. In conclusion, our study implicates TET1 as a vital epigenetic regulator contributing to chronic inflammatory TMJ pain via trigeminal TNFα signaling. Targeting TET1 holds promise for epigenetic interventions in TMJ pain management.

Cuproptosis-Associated lncRNA Gene Signature Establishes New Prognostic Profile and Predicts Immunotherapy Response in Endometrial Carcinoma.

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment. METHODS: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. RESULTS: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. CONCLUSIONS: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic.

Antigen-loaded flagellate bacteria for enhanced adaptive immune response by intradermal injection.

Since the skin limits the distribution of intradermal vaccines, a large number of dendritic cells in the skin cannot be fully utilized to elicit a more effective immune response. Here, we loaded the antigen to the surface of the flagellate bacteria that was modified by cationic polymer, thus creating antigen-loaded flagellate bacteria (denoted as 'FB-Ag') to overcome the skin barrier and perform the active delivery of antigen in the skin. The FB-Ag showed fast speed (∼0.2 µm s-1) and strong dendritic cell activation capabilities in the skin model in vitro. In vivo, the FB-Ag promoted the spread of antigen in the skin through active movement, increased the contact between Intradermal dendritic cells and antigen, and effectively activated the internal dendritic cells in the skin. In a mouse of pulmonary metastatic melanoma and in mice bearing subcutaneous melanoma tumor, the FB-Ag effectively increased antigen-specific therapeutic efficacy and produced long-lasting immune memory. More importantly, the FB-Ag also enhanced the level of COVID-19 specific antibodies in the serum and the number of memory B cells in the spleen of mice. The movement of antigen-loaded flagellate bacteria to overcome intradermal constraints may enhance the activation of intradermal dendritic cells, providing new ideas for developing intradermal vaccines.

Defining nomograms for predicting prognosis of early and late recurrence in gastric cancer patients after radical gastrectomy.

There are few studies on the predictive factors of early recurrence (ER) and late recurrence (LR) of advanced gastric cancer (GC) after curative surgery. Our study aims to explore the independent predictors influencing the prognosis between ER and LR in patients with advanced GC after curative intent surgery respectively. And we will further develop nomograms for prediction of post recurrence survival (PRS). Data of patients with GC who received radical gastrectomy was retrospectively collected. Recurrence was classified into ER and LR according to the 2 years after surgery as the cutoff value. Multivariate Cox regression analyses were used to explore significant predictors in our analysis. Then these significant predictors were integrated to construct nomograms. The 1-, 2- and 3-year probabilities of PRS in patients with ER were 30.00%, 16.36% and 11.82%, respectively. In contrast, the late group were 44.68%, 23.40%, and 23.30%, respectively. Low body mass index (hazard ratio [HR] = 0.86, P = .001), elevated monocytes count (HR = 4.54, P = .003) and neutrophil-lymphocyte ratio (HR = 1.03, P = .037) at the time of recurrence were risk factors of PRS after ER. Decreased hemoglobin (HR = 0.97, P = .008) and elevated neutrophil-lymphocyte ratio (HR = 1.06, P = .045) at the time of recurrence were risk factors of PRS after LR. The calibration curves for probability of 1-, 2-, and 3-year PRS showed excellent predictive effect. Internal validation concordance indexes of PRS were 0.722 and 0.671 for ER and LR respectively. In view of the different predictive factors of ER and LR of GC, the practical predictive model may help clinicians make reasonable decisions.

Gut-Brain Crosstalk and the Central Mechanisms of Orofacial Pain.

Accumulated evidence has demonstrated that the gut microbiome can contribute to pain modulation through the microbiome-gut-brain axis. Various relevant microbiome metabolites in the gut are involved in the regulation of pain signaling in the central nervous system. In this review, we summarize recent advances in gut-brain interactions by which the microbiome metabolites modulate pain, with a focus on orofacial pain, and we further discuss the role of gut-brain crosstalk in the central mechanisms of orofacial pain whereby the gut microbiome modulates orofacial pain via the vagus nerve-mediated direct pathway and the gut metabolites/molecules-mediated indirect pathway. The direct and indirect pathways both contribute to the central regulation of orofacial pain through different brain structures (such as the nucleus tractus solitarius and the parabrachial nucleus) and signaling transmission across the blood-brain barrier, respectively. Understanding the gut microbiome-regulated pain mechanisms in the brain could help us to develop non-opioid novel therapies for orofacial pain.

Fabricating s-collidine-derived vinylene-linked covalent organic frameworks for photocatalysis.

Research into vinyl-linked covalent organic frameworks (COFs) has grown significantly in recent years due to various attractive properties. Herein, we design and synthesize two highly crystalline and stable 2,4,6-collidine-derived vinylene-linked 2D COFs. Both COFs can act as efficient photocatalysts to facilitate visible-light-driven aerobic oxidation. The TM-TBT-COF was observed to exhibit superior activity and recyclability owing to its excellent semiconducting properties.

Translation of interacting cavitation bubble in a plane acoustic field.

In a plane acoustic field, a model involving the radial and translational motions of bubble is derived, which is used to numerically investigate the translation of two interacting spherical cavitation bubbles. For the smaller initial distance between bubble centers, we investigate the dynamics of two bubbles, and find that they could come into contact but the velocities of closing to each other are different when the equilibrium radius is different. The results show that when the wavelength of plane acoustic field is much larger than the initial distance, the bubbles are approximately pulsating in phase. Moreover, the velocity of contact process of two bubbles can be changed by adjusting the parameters of plane acoustic field. For increasing in the initial distance, the bubbles would present two translation motions: close to each other for the pulsating in phase and away from each other for the pulsating out of phase, which could be verified by calculating the secondary Bjerknes force. Meanwhile, the larger the initial distance, the smaller the secondary Bjerknes force value is. Understanding the translation of bubble is of great significance for helpful explaining formation of streamer structures in ultrasonic cavitation.

Long-term and liver-selected ginsenoside C-K nanoparticles retard NAFLD progression by restoring lipid homeostasis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent hepatic disease characterized as lipid accumulation, yet without any approved drug. And development of therapeutic molecules is obstructed by low efficiency and organ toxicity. Herein, we develop a long-term, low-toxic and liver-selected nano candidate, nabCK, to alleviate NAFLD. NabCK is simply composed by natural compound ginsenoside compound K (CK) and albumin. As a major metabolite of ginseng, ginsenoside CK has excellently modulating functions for lipid metabolism, but accompanied by an extremely poor bioavailability <1%. Albumin is a key lipid carrier secreted and metabolized by livers. Thereby, it can improve solubility and liver-localization of CK. In adipocytes and hepatocytes, nabCK prevents lipid deposition and eliminates lipid droplets. Transcriptomic analysis reveals that nabCK rectifies various pathways that involved in steatosis development, including lipid absorption, lipid export, fatty acid biosynthesis, lipid storage and inflammation. All these pathways are modulated by mTOR, the pivotal feedback sensor that is hyperactive in NAFLD. NabCK suppresses mTOR activation to restores lipid homeostasis. In high-fat diet (HFD) induced NAFLD mice, nabCK retards development of steatosis and fibrosis, coupling a protective effect on cardiac tissues from lipotoxicity. Together, nabCK is a safe and potent candidate to offer benefits for NAFLD treatment.

Perfluorotributylamine-Loaded Albumin Nanoparticles Downregulate Platelet-Derived TGFß to Inhibit Tumor Metastasis.

Tumor metastasis contributes to the low overall survival of tumor patients, while transforming growth factor-ß (TGFß) has been recognized as a prominently promoting factor in the development of tumor metastasis. Platelets reserve abundant TGFß, which will be secreted to peripheral blood after activation, and they are the dominant source of circulating TGFß. Therefore, downregulation of platelet-derived TGFß is expected to inhibit the metastasis of circulating tumor cells. Here, unfolded human serum albumin (HSA)-coated perfluorotributylamine (PFTBA) nanoparticles were constructed to display a favorable platelet delivery and an antiplatelet effect to downregulate platelet-derived TGFß in vitro and in blood plasma. PFTBA@HSA-mediated TGFß downregulation impaired epithelial-mesenchymal transition of tumor cells as well as their migration and invasion behaviors and enhanced immune surveillance of NK cells. Intravenous injection of PFTBA@HSA effectively reduced tumor metastasis on the lungs or liver to improve the survival rate of mice on multiple metastatic models, including CT26 colon cancer, B16F10 melanoma, and 4T1 breast cancer. Compared with the clinical antiplatelet drug ticagrelor, PFTBA@HSA reduced bleeding risk when displaying a favorable downregulation on platelet-derived TGFß, thereby obtaining a higher therapy benefit. Together, this study confirmed that downregulation of platelet-derived TGFß by PFTBA@HSA will be a potential approach and therapeutic candidate for the prevention of tumor metastasis.

A female-specific role for trigeminal dynorphin in orofacial pain comorbidity.

ABSTRACT: Migraine is commonly reported in patients with temporomandibular disorders (TMDs), but little is known about the mechanisms underlying the comorbid condition. Here, we prepared a mouse model to investigate this comorbidity, in which masseter muscle tendon ligation (MMTL) was performed to induce a myogenic TMD, and the pre-existing TMD enabled a subthreshold dose of nitroglycerin (NTG) to produce migraine-like pain in mice. RNA sequencing followed by real-time quantitative polymerase chain reaction confirmation showed that MMTL plus NTG treatment increased prodynorphin ( Pdyn ) mRNA expression in the spinal trigeminal nucleus caudalis (Sp5C) of female mice but not in male mice. Chemogenetic inhibition of Pdyn -expressing neurons or microinjection of antidynorphin antiserum in the Sp5C alleviated MMTL-induced masseter hypersensitivity and diminished the MMTL-enabled migraine-like pain in female mice but not in male mice. Moreover, chemogenetic activation of Pdyn -expressing neurons or microinjection of dynorphin A (1-17) peptide in the Sp5C enabled a subthreshold dose of NTG to induce migraine-like pain in female mice but not in male mice. Taken together, our results suggest that trigeminal dynorphin has a female-specific role in the modulation of comorbid TMDs and migraine.

Phylogenetic Analysis of Some Species of the Anopheles hyrcanus Group (Diptera: Culicidae) in China Based on Complete Mitochondrial Genomes.

Some species of the Hyrcanus group are vectors of malaria in China. However, the member species are difficult to identify accurately by morphology. The development of sequencing technologies offers the possibility of further studies based on the complete mitochondrial genome. In this study, samples of mosquitoes of the Hyrcanus group were collected in China between 1997 and 2015. The mitochondrial genomes of ten species of the Hyrcanus group were analyzed, including the structure and base composition, codon usage, secondary structure of tRNA, and base difference sites in protein coding regions. Phylogenetic analyses using maximum-likelihood and Bayesian inference were performed based on mitochondrial genes and complete mitochondrial genomes The mitochondrial genome of 10 Hyrcanus group members ranged from 15,403 bp to 15,475 bp, with an average 78.23% (A + T) content, comprising of 13 PCGs (protein coding genes), 22 tRNAs, and 2 rRNAs. Site differences between some closely related species in the PCGs were small. There were only 36 variable sites between Anopheles sinensis and Anopheles belenrae for a variation ratio of 0.32% in all PCGs. The pairwise interspecies distance based on 13 PCGs was low, with an average of 0.04. A phylogenetic tree constructed with the 13 PCGs was consistent with the known evolutionary relationships. Some phylogenetic trees constructed by single coding regions (such as COI or ND4) or combined coding regions (COI + ND2 + ND4 + ND5 or ND2 + ND4) were consistent with the phylogenetic tree constructed using the 13 PCGs. The phylogenetic trees constructed using some coding genes (COII, ND5, tRNAs, 12S rRNA, and 16S rRNA) differed from the phylogenetic tree constructed using PCGs. The difference in mitochondrial genome sequences between An. sinensis and An. belenrae was very small, corresponding to intraspecies difference, suggesting that the species was in the process of differentiation. The combination of all 13 PCG sequences was demonstrated to be optimal for phylogenetic analysis in closely related species.