Combining Anti-epidermal Growth Factor Receptor (EGFR) Therapy with Immunotherapy in Metastatic Colorectal Cancer (mCRC).

INTRODUCTION: Monoclonal antibodies binding the EGFR, such as cetuximab and panitumumab, have been extensively used as targeted therapy for the treatment of mCRC. However, in clinical practice, it has been found that these treatment options have some limitations and fail to fully exploit their immunoregulatory activities. Meanwhile, because of the limited effects of current treatments, immunotherapy is being widely studied for patients with mCRC. However, previous immunotherapy trials in mCRC patients have had unsatisfactory outcomes as monotherapy. Thus, combinatorial treatment strategies are being researched. AREAS COVERED: The authors retrieved relevant documents of combination therapy for mCRC from PubMed and Medline. This review elaborates on the knowledge of immunomodulatory effects of anti-EGFR therapy alone and in combination with immunotherapy for mCRC. EXPERT OPINION: Although current treatment options have improved median overall survival (OS) for advanced disease to 30 months, the prognosis remains challenging for those with metastatic disease. More recently, the combination of anti-EGFR therapy with immunotherapy has been shown activity with complementary mechanisms. Hence, anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC.

Melatonin Attenuates Sepsis-Induced Acute Lung Injury via Inhibiting Excessive Mitophagy.

Background: Epidemiological studies have indicated that lung injury is a frequent complication of sepsis. Mitophagy is vital to multiple pathological processes and diseases; however, its influence on sepsis-induced acute lung injury remains elusive. Melatonin has multiple antioxidant action and anti-inflammatory effects, including regulating mitophagy and inflammatory cytokine expression. Whereas, little is known about the affection of melatonin and mitophagy on CLP-induced ALI. Methods: The in vivo effect of melatonin on OPTN-mediated mitophagy was studied by CLP-induced ALI in a mouse model using C57BL/6 followed by treatment with vehicle and melatonin (30 mg/kg/d, intraperitoneal injection). ALI was assayed by lung wet /dry ratio, hematoxylin and eosin staining, and immunohistochemical staining. Signaling pathway changes were subsequently determined by Western blotting and immunofluorescence staining. The effects of melatonin on STAT3 activation and TNF-α production were detected by Western blotting, PCR, and immunohistochemical staining. Results: Our results indicated that OPTN, mitophagy adaptors were significantly repressed in CLP-induced ALI, accompanied by overactivation of mitophagy and inflammation. At the same time, we found that melatonin treatment alleviated ALI caused by CLP, and the effect was highly correlated with OPTN-related mitophagy. Furthermore, we demonstrated that OPTN-related mitophagy, which was normalized by melatonin, blocked STAT3 involved epithelial barrier and inflammation in vivo. Conclusion: Overall, our results confirm that mitophagy is adjusted by melatonin in the CLP-induced ALI. Moreover, manipulation of mitophagy through melatonin could be a possible treatment to reduce sepsis-associated lung injury.

Long-term care status for the elderly with different levels of physical ability: a cross-sectional survey in first-tier cities of China.

BACKGROUND: Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. METHODS: This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients' needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann-Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. RESULTS: Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants' basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. CONCLUSIONS: The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. TRIAL REGISTRATION: The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).

Aligned Electroactive Electrospun Fibrous Scaffolds for Peripheral Nerve Regeneration.

Effective repair and functional recovery of large peripheral nerve deficits are urgent clinical needs. A biofunctional electroactive scaffold typically acts as a "bridge" for the repair of large nerve defects. In this study, we constructed a biomimetic piezoelectric and conductive aligned polypyrrole (PPy)/polydopamine (PDA)/poly-l-lactic acid (PLLA) electrospun fibrous scaffold to improve the hydrophilicity and cellular compatibility of PLLA and restore the weakened piezoelectric effect of PDA, which is beneficial in promoting Schwann cell differentiation and dorsal root ganglion neuronal extension and alignment. The aligned PPy/PDA/PLLA fibrous scaffold bridged the sciatic nerve of Sprague-Dawley rats with a 10 mm deficit, prevented autotomy, and promoted nerve regeneration and functional recovery, thereby activating the calcium and AMP-activated protein kinase signaling pathways. Therefore, electroactive fibrous scaffolds exhibit great potential for neural tissue regeneration.

A Bioinspired Self-Healing Conductive Hydrogel Promoting Peripheral Nerve Regeneration.

The development of self-healing conductive hydrogels is critical in electroactive nerve tissue engineering. Typical conductive materials such as polypyrrole (PPy) are commonly used to fabricate artificial nerve conduits. Moreover, the field of tissue engineering has advanced toward the use of products such as hyaluronic acid (HA) hydrogels. Although HA-modified PPy films are prepared for various biological applications, the cell-matrix interaction mechanisms remain poorly understood; furthermore, there are no reports on HA-modified PPy-injectable self-healing hydrogels for peripheral nerve repair. Therefore, in this study, a self-healing electroconductive hydrogel (HASPy) from HA, cystamine (Cys), and pyrrole-1-propionic acid (Py-COOH), with injectability, biodegradability, biocompatibility, and nerve-regenerative capacity is constructed. The hydrogel directly targets interleukin 17 receptor A (IL-17RA) and promotes the expression of genes and proteins relevant to Schwann cell myelination mainly by activating the interleukin 17 (IL-17) signaling pathway. The hydrogel is injected directly into the rat sciatic nerve-crush injury sites to investigate its capacity for nerve regeneration in vivo and is found to promote functional recovery and remyelination. This study may help in understanding the mechanism of cell-matrix interactions and provide new insights into the potential use of HASPy hydrogel as an advanced scaffold for neural regeneration.

Unraveling genomic regions and candidate genes for multiple disease resistance in upland cotton using meta-QTL analysis.

Verticillium wilt (VW), Fusarium wilt (FW) and Root-knot nematode (RKN) are the main diseases affecting cotton production. However, many reported quantitative trait loci (QTLs) for cotton resistance have not been used for agricultural practices because of inconsistencies in the cotton genetic background. The integration of existing cotton genetic resources can facilitate the discovery of important genomic regions and candidate genes involved in disease resistance. Here, an improved and comprehensive meta-QTL analysis was conducted on 487 disease resistant QTLs from 31 studies in the last two decades. A consensus linkage map with genetic overall length of 3006.59 cM containing 8650 markers was constructed. A total of 28 Meta-QTLs (MQTLs) were discovered, among which nine MQTLs were identified as related to resistance to multiple diseases. Candidate genes were predicted based on public transcriptome data and enriched in pathways related to disease resistance. This study used a method based on the integration of Meta-QTL, known genes and transcriptomics to reveal major genomic regions and putative candidate genes for resistance to multiple diseases, providing a new basis for marker-assisted selection of high disease resistance in cotton breeding.

[Causes and prognosis analysis of hyperdynamic left ventricular ejection fraction in intensive care unit patients with sepsis].

OBJECTIVE: To analyze the causes of hyperdynamic left ventricular ejection fraction (LVEF) in sepsis patients in the intensive care unit (ICU) and its impact on prognosis. METHODS: A retrospective cohort study was conducted. The clinical data of 273 sepsis patients admitted to the department of critical care medicine of the Affiliated People's Hospital of Jiangsu University from January 2018 to October 2021 were collected including gender, age, severity score, comorbidities, source of infection, vital signs, transthoracic echocardiographic (TTE) parameters, fluid intake and output, vasoactive drug dose, therapeutic measures and prognostic indicators. The patients were divided into normal LVEF group (LVEF 0.55-0.70), low LVEF group (LVEF < 0.55) and hyperdynamic LVEF group (LVEF > 0.70) according to the TTE examination results within 7 days of ICU admission. The clinical indicators among the three groups were compared and analyzed, and multivariate Logistic regression analysis was used to screen risk factors for the development of hyperdynamic LVEF in patients with sepsis. Spearman correlation analysis was used to determine the correlation between the mortality of different types of LVEF and clinical variables. RESULTS: Among 273 patients, 20 patients with severe valvular or cardiomyopathy at admission and those who did not completed cardiac ultrasound within 7 days of ICU admission were excluded. A total of 253 patients were finally enrolled, including 169 patients in the normal LVEF group, 40 patients in the low LVEF group, and 44 patients in the hyperdynamic LVEF group. There were statistically significant differences in age, sequential organ failure assessment (SOFA) score, central venous pressure (CVP), heart rate (HR), oxygenation index (PaO2/FiO2), blood lactate (Lac), urine output, vasoactive drug dose, ratio of hypertension, ischemic heart disease, chronic liver disease, cancer, invasive mechanical ventilation and renal replacement therapy (RRT), and incidence of septic shock among the different types of LVEF groups. TTE results analysis showed that the hyperdynamic LVEF group had higher stroke volume (SV) and cardiac index (CI) than those in the normal LVEF and low LVEF groups, lower systemic vascular resistance (SVR) than that in the normal LVEF and low LVEF groups, and an increased E/A ratio. The 90-day mortality in the hyperdynamic LVEF group was significantly higher than that in the normal LVEF and low LVEF groups [59.1% (26/44) vs. 24.9% (42/169), 32.5% (13/40), both P < 0.05]. Multivariate Logistic regression analysis showed that chronic liver disease [odds ratio (OR) = 1.712, 95% confidence interval (95%CI) was 0.912-3.234, P < 0.001], cancer (OR = 2.784, 95%CI was 1.296-6.151, P < 0.001), HR (OR = 1.026, 95%CI was 1.014-1.038, P < 0.001), vasoactive drug dose (OR = 1.133, 95%CI was 1.009-1.291, P < 0.001), and invasive mechanical ventilation (OR = 2.141, 95%CI was 1.285-3.651, P < 0.001) were independent factors for hyperdynamic LVEF in ICU sepsis patients. Correlation analysis showed that the mortality of hyperdynamic LVEF, normal LVEF and low LVEF patients was positively correlated with vasoactive drug dose (r value was 0.251, 0.361, 0.289, respectively, all P < 0.001). The mortality of the hyperdynamic LVEF patients was negatively correlated with SVR (r = -0.545, P < 0.001). CONCLUSIONS: Chronic liver disease, cancer, HR, vasoactive drugs dose, and invasive mechanical ventilation are independent risk factors for hyperdynamic LVEF in patients with sepsis. Hyperdynamic LVEF is positively associated with mortality in sepsis patients, which may be due to the the decrease of SVR caused by septic vascular paralysis.

Dapagliflozin attenuates cardiac remodeling and dysfunction in rats with ß-adrenergic receptor overactivation through restoring calcium handling and suppressing cardiomyocyte apoptosis.

Background: Long-term ß-adrenergic receptor (ß-AR) activation can impair myocardial structure and function. Dapagliflozin (DAPA) has been reported to improve clinical prognosis in heart failure patients, whereas the exact mechanism remains unclear. Here, we investigated the effects of DAPA against ß-AR overactivation toxicity and explored the underlying mechanism.Methods and Results: Rats were randomized to receive saline + placebo, isoproterenol (ISO, 5 mg/kg/day, intraperitoneally) + placebo, or ISO + DAPA (1 mg/kg/day, intragastrically) for 2-week. DAPA treatment improved cardiac function, alleviated myocardial fibrosis, prevented cardiomyocytes (CMs) apoptosis, and decreased the expression of ER stress-mediated apoptosis markers in ISO-treated hearts. In isolated CMs, 2-week ISO stimulation resulted in deteriorated kinetics of cellular contraction and relaxation, increased diastolic intracellular Ca2+ level and decay time constant of Ca2+ transient (CaT) but decreased CaT amplitude and sarcoplasmic reticulum (SR) Ca2+ level. However, DAPA treatment prevented abnormal Ca2+ handling and contractile dysfunction in CMs from ISO-treated hearts. Consistently, DAPA treatment upregulated the expression of SR Ca2+-ATPase protein and ryanodine receptor 2 (RyR2) but reduced the expression of phosphorylated-RyR2, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated-CaMKII in ventricles from ISO-treated rats.Conclusion: DAPA prevented myocardial remodeling and cardiac dysfunction in rats with ß-AR overactivation via restoring calcium handling and suppressing ER stress-related CMs apoptosis.

LncRNA PVT1 promotes strong stemness and endothelial progenitor cell characteristics in renal carcinoma stem cells.

Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells-like (EPCs-like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs-like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR-15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC.

Neuronal Connectivity as a Determinant of Cell Types and Subtypes.

Classifications of single neurons at brain-wide scale is a powerful way to characterize the structural and functional organization of a brain. We acquired and standardized a large morphology database of 20,158 mouse neurons, and generated a whole-brain scale potential connectivity map of single neurons based on their dendritic and axonal arbors. With such an anatomy-morphology-connectivity mapping, we defined neuron connectivity types and subtypes (both called "c-types" for simplicity) for neurons in 31 brain regions. We found that neuronal subtypes defined by connectivity in the same regions may share statistically higher correlation in their dendritic and axonal features than neurons having contrary connectivity patterns. Subtypes defined by connectivity show distinct separation with each other, which cannot be recapitulated by morphology features, population projections, transcriptomic, and electrophysiological data produced to date. Within this paradigm, we were able to characterize the diversity in secondary motor cortical neurons, and subtype connectivity patterns in thalamocortical pathways. Our finding underscores the importance of connectivity in characterizing the modularity of brain anatomy, as well as the cell types and their subtypes. These results highlight that c-types supplement conventionally recognized transcriptional cell types (t-types), electrophysiological cell types (e-types), and morphological cell types (m-types) as an important determinant of cell classes and their identities.

Polymorphisms and NIHL: a systematic review and meta-analyses.

Background: Noise-induced hearing loss (NIHL) has always been a global public health problem, which is related to noise exposure and genetic factors. Many researchers have tried to identify the polymorphisms that cause different individuals' susceptibility to NIHL. We conducted a meta-analysis of the most frequently studied polymorphisms to identify those genes that may be associated with NIHL and may provide value in risk prevention. Methods: PubMed, China National Knowledge Infrastructure (CNKI) database, Embase, Wang Fang, Web of Science and Cochrane library were searched, and qualified studies on the correlation between polymorphism and NIHL susceptibility were screened, and then polymorphisms cited in at least three studies were selected for meta-analysis. Fixed- or random-effects models were used to calculate odds ratios and 95% confidence intervals. Statistical I2 tests and sensitivity analyses were used to detect interstudy heterogeneity and test the statistical stability of overall estimates, respectively. Egger's tests were applied to detect publication bias among included studies. All of the above analyses were performed using stata 17.0. Results: 64 genes were initially selected and introduced in 74 papers. Among them, 10 genes (and 25 polymorphisms) have been reported in more than 3 papers. Twenty five polymorphisms participated in the meta-analysis. Of the 25 polymorphisms, only 5 were significantly associated with the risk of AR: rs611419 (GRHL2) polymorphism and rs3735715 polymorphism (GRHL2), rs208679 polymorphism (CAT), rs3813346 polymorphism (EYA4) were significantly associated with the susceptibility of NIHL, rs2227956 polymorphism (HSP70) was significantly associated with the susceptibility of white population NIHL, and the remaining 20 gene polymorphisms were not significantly associated with NIHL. Conclusion: We found polymorphisms that are valuable for the prevention of NIHL and polymorphisms that are not related to NIHL. This is the first step to establish an effective risk prediction system for the population, especially for high-risk groups, which may help us better identify and prevent the occurrence of NIHL. In addition, our research results contribute to the in-depth exploration of NIHL. Systematic review registration: https://inplasy.com/inplasy-2023-6-0003/, identifier INPLASY202360003.

Effectiveness of Halo-Pelvic Traction and Thoracoplasty for Pulmonary Artery Pressure and Cardiopulmonary Function in Patients With Severe Spinal Deformity.

STUDY DESIGN: Retrospective review. OBJECTIVE: To evaluate the effectiveness of halo-pelvic traction and thoracoplasty for pulmonary artery pressure (PAP) and cardiopulmonary function in patients with severe spinal deformity. SUMMARY OF BACKGROUND DATA: The effect of severe spinal deformity on pulmonary arterial hypertension, cardiac structure, and function has received little attention before. PATIENTS AND METHODS: A total of 21 patients with severe spinal deformity were included in our study; all patients were examined by echocardiography and pulmonary function test before and after treatment. The correlations between PAP and pulmonary function were examined using Pearson correlation analysis. RESULTS: The PAP decreased from 58.67 ± 20.24 to 39.00 ± 12.51 mm Hg, and the PAP of 42.86% of the patients returned to normal after treatment. Right cardiac enlargement, left ventricular diastolic function, and pulmonary function were improved at the same time. The ratio of left ventricular to right ventricular diameter returned to normal. Moderate correlations (correlation coefficient: -0.513 to -0.559) between PAP and forced vital capacity and forced expiratory volume in the first second were identified. CONCLUSIONS: Pulmonary arterial hypertension, ventricular diastolic function, and pulmonary function were improved after halo-pelvic traction and thoracoplasty. A moderate negative correlation was identified between PAP and pulmonary function: the more pulmonary function improved, the more PAP decreased.

HSPB8 up-regulation alleviates cognitive dysfunction in a mouse model of sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is associated with a higher risk of cognitive deficits; however, its potential mechanisms are still unknow. Recently, researches show that HSPB8, a family of small heat shock proteins, affects cognitive function and ameliorates sepsis-induced dysfunction. However, the role of HSPB8 in SAE-associated cognitive impairment has not been elucidated. In this study, we found that HSPB8 expression was up-regulated in the brain of mice with lipopolysaccharide-induced sepsis. HSPB8 overexpression alleviated cognitive decline in SAE mice. In addition, exogenous HSPB8 exerts neuroprotective effects and salvages synaptic function via regulating NRF1/TFAM-induced mitochondrial biogenesis and DRP1-mediate mitochondrial fission in a lipopolysaccharide-induced mouse model. Furthermore, HSPB8 overexpression inhibits IBA1 and NLRP3 activation in the SAE model. Overexpression of HSPB8 may be an efficient treatment for relieving SAE-related cognitive decline.

Overexpressed CD44 is associated with B-cell activation via the HA-CD44-AIM2 pathway in lupus B cells.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by aberrant development of B cells and excess production of autoantibodies. Our team previously reported that absent in melanoma 2 (AIM2) regulates B-cell differentiation via the Bcl-6-Blimp-1 axis. Notably, in keyhole limpet hemocyanin (KLH)-immunized CD19creAim2f/f mice, the frequency of CD19+CD44+ B cells was decreased, accompanied by a weakened KLH response, indicating that AIM2 deficiency suppressed the antigen-induced B-cell immune response by downregulating the expression of CD44. CD44, a surface marker of T-cell activation and memory, was overexpressed in T cells of SLE patients, but its roles and mechanism in B cells have not been elucidated. In the current work, we revealed that CD44 expression was upregulated in the B cells of SLE patients and MRL/lpr mice, accompanied by elevated AIM2 expression in CD19+CD44+ B-cell subsets, and that its ligand hyaluronan (HA) was also abnormally increased in the serum of SLE patients. Notably, the extrafollicular (EF) region serves as an important site of B-cell activation and differentiation separate from the germinal center, while CD44 expression is concentrated in EF B cells. In addition, in vitro experiments demonstrated that the HA-CD44 interaction stimulated B-cell activation and upregulated the expression of AIM2 and the transcription factor STAT3. Either blocking CD44, knocking down AIM2 expression or suppressing the activity of STAT3 in B cells suppressed B-cell activation and proliferation. Moreover, blocking CD44 downregulated the expression of STAT3 and AIM2, while suppressing the activity of STAT3 decreased the expression of CD44 and AIM2. In summary, overexpressed CD44 in B cells might participate in B-cell activation and proliferation in the EF region via the HA-CD44-AIM2 pathway, providing potential targets for SLE therapy.

Discovery of 2-(Methylcarbonylamino) thiazole as PDE4 inhibitors via virtual screening and biological evaluation.

Phosphodiesterase-4, the primary enzyme responsible for cAMP degradation in the majority of immune and inflammatory cells, plays a critical role in the regulation of intracellular cAMP levels. Consequently, small molecular entities capable of inhibiting PDE4 have been employed in the treatment of inflammation-associated disorders, such as chronic obstructive pulmonary disease (COPD), psoriasis, atopic dermatitis (AD), inflammatory bowel diseases (IBD), rheumatic arthritis (RA). In the present investigation, a multi-faceted approach was employed to identify novel PDE4 inhibitors, utilizing the co-crystallization structure of PDE4B available in the Protein Data Bank (PDB) database, drug-like screening, false positive filtration, similarity and ADMET screen, as well as molecular docking via multiple software platforms, in conjunction with bioactivity assays. A thiazol-3-propanamides derivative, designated MR9, was discovered to inhibit PDE4B activity with IC50 values of 2.12 µM and suppress cellular inflammatory factor TNF-α release with an EC50 value of 3.587 µM. These findings suggest that the innovative active scaffold of MR9 offers a promising foundation for further structural refinement aimed at developing more potent PDE4 inhibitors.

The mediating effect of financial development on CO2 emissions: An empirical study based on provincial panel data in China.

Global climate change has become the greatest threat to humanity, and China is developing policies among various industries to peak CO2 emissions as soon as possible and expects the reduction of CO2 emissions through financial development. Based on the panel data of 30 provinces in China from 2000 to 2017, this paper uses fixed effect model and mediating effect model to explore the mechanism and effective pathway of financial development on CO2 emissions per capita among different regions in China. Empirical results consistently indicate that financial development has the significantly positive effect on CO2 emissions per capita, but the impact is inverted U-shaped. It means that only when the financial development in China gradually increased to 4.21 can achieve the goal of reducing CO2 emissions per capita. These results provide new explanatory ideas for the inconsistent direction of the impact of financial development on carbon emissions in existing studies. Then, the technological innovation and industrial structure are intermediaries for financial development to reduce CO2 emissions per capita, while the economic scale is the opposite. And it illustrates not only theoretical but also empirical results on the mediating pathways of financial development driven CO2 emission reduction. Under the theory of "natural resource curse", in regions with high fossil energy dependence, the mediating effect of the economic scale is greater than that in regions with low fossil energy dependence. But the mediating effects of technological innovation and industrial structure from financial development on CO2 emissions per capita are all negative and more powerful than that in regions with low fossil energy dependence. This provides an important practical basis for the development of differentiated carbon reduction policies through finance in different fossil energy dependent regions.

Development of a synchronous recording and photo-stimulating electrode in multiple brain neurons.

The investigation of brain networks and neural circuits involves the crucial aspects of observing and modulating neurophysiological activity. Recently, opto-electrodes have emerged as an efficient tool for electrophysiological recording and optogenetic stimulation, which has greatly facilitated the analysis of neural coding. However, implantation and electrode weight control have posed significant challenges in achieving long-term and multi-regional brain recording and stimulation. To address this issue, we have developed a mold and custom-printed circuit board-based opto-electrode. We report successful opto-electrode placement and high-quality electrophysiological recordings from the default mode network (DMN) of the mouse brain. This novel opto-electrode facilitates synchronous recording and stimulation in multiple brain regions and holds promise for advancing future research on neural circuits and networks.

Application of Biophysical Properties of Meridians in the Visualization of Pericardium Meridian.

Background: The biophysical properties of the meridian system, an important concept of traditional Chinese medicine, include low impedance, resounding voice, and high acoustic conductance, all of which are helpful for elucidating the essence of meridians. Objectives: To visualize the human pericardium meridian (PC) based on the resounding voice property of meridians. Methods: Visualization of the PC was performed by injection of fluorescein sodium at the PC6 acupoint (Neiguan) on the PC. Before injection, percussion active points (PAPs) were identified by the virtue of their resounding voice properties. After injection, the trajectories of fluorescein migration throughout the body surface were recorded and analyzed. The distribution of fluorescein in the tissue was further studied using cross-sections of hind limbs of mini-pigs, in which fluorescein was injected into low impedance points. Results: The identified PAP lines were colocalized with PC. Following intradermal fluorescein injection, 1-3 fluorescent lines, which were unrelated to the arm veins, were observed in 7 of 10 participants; 85.4% of fluorescent signals were coincident with PAPs and their intensity had a negative correlation with the body mass index (r = -0.56, p = 0.045). Cross-sections showed a Y-shaped fluorescence pattern where the two migration lines on the surface were the two vertices of the "Y." Conclusion: The trajectories of fluorescein in the body are suggestive of the anatomical structure of meridians. The PC is related to the deep horizontal interstitial channels that connect to the body surface through vertical interstitial spaces. These biophysical properties and techniques for meridian visualization are valuable for revealing the anatomical structure of meridians.

Validation of the Longshi scale in assessment of function in patients from different economic, educational and regional backgrounds in China.

OBJECTIVE: This study validates performance of the Longshi scale against modified Barthel index in assessment of function in patients from different economic, educational and regional backgrounds in China. DESIGN: This is a cross-sectional study. SETTING: One hundred and three hospitals and rehabilitation institutions across China. PARTICIPANTS: A total of 14,752 patients with physical and cognitive impairments were enrolled and classified to five educational levels and five family income levels; 8060 participants were further selected from five regions to study regional influences. MAIN MEASURES: Activities of daily living were assessed with two evaluation tools, the Longshi scale and modified Barthel index. Results of evaluation with Longshi scale performed by non-healthcare workers were validated against modified Barthel index performed by healthcare workers using Pearson's correlation test. RESULTS: There were significant positive correlations between the findings of the Longshi scale administered by non-healthcare professionals and the modified Barthel index administered by healthcare professionals. This was true for level of education (correlations ranged from 0.697 to 0.822), family income level (correlations ranged from 0.724 to 0.761) and region (correlations ranged from 0.737 to 0.776). CONCLUSION: In a large dataset of 14,752 patients, positive correlations were found between Longshi scale and modified Barthel index measures of function. Positive correlations persisted across subgroup analysis of groups from different social, economic and regional backgrounds, and with administration by non-healthcare professionals. CLINICAL TRIAL REGISTRATION: ChiCTR2000034067, www.chictr.org.cn.

GhSINA1, a SEVEN in ABSENTIA ubiquitin ligase, negatively regulates fiber development in Upland cotton.

Protein ubiquitination is essential for plant growth and responses to the environment. The SEVEN IN ABSENTIA (SINA) ubiquitin ligases have been extensively studied in plants, but information on their roles in fiber development is limited. Here, we identified GhSINA1 in Upland cotton (Gossypium hirsutum), which has a conserved RING finger domain and SINA domain. Quantitative real-time PCR (qRT-PCR) analysis showed that GhSINA1 was preferentially expressed during fiber initiation and elongation, especially during initiation in the fuzzless-lintless cotton mutant. Subcellular localization experiments indicated that GhSINA1 localized to the nucleus. In vitro ubiquitination analysis revealed that GhSINA1 has E3 ubiquitin ligase activity. Ectopic overexpression of GhSINA1 in Arabidopsis thaliana reduced the number and length of root hairs and trichomes. Yeast two-hybrid (Y2H), firefly luciferase complementation imaging (LCI), and bimolecular fluorescence complementation (BiFC) assays demonstrated that the GhSINA1 proteins could interact with each other to form homodimers and heterodimers. Overall, these results suggest that GhSINA1 may act as a negative regulator in cotton fiber development through homodimerization and heterodimerization.