Mechanisms Of Differentiation Research Articles

Metabolic and Transcriptomic Profile Revealing the Differential Accumulating Mechanism in Different Parts of Dendrobium nobile

Metabolic and Transcriptomic Profile Revealing the Differential Accumulating Mechanism in Different Parts of Dendrobium nobile

Sarcomatoid and Rhabdoid Renal Cell Carcinoma: Clinical, Pathologic, and Molecular Genetic Features.

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.

The role of semaphorin 3A on chondrogenic differentiation.

Osteoblast-derived semaphorin3A (Sema3A) has been reported to be involved in bone protection, and Sema3A knockout mice have been reported to exhibit chondrodysplasia. From these reports, Sema3A is considered to be involved in chondrogenic differentiation and skeletal formation, but there are many unclear points about its function and mechanism in chondrogenic differentiation. This study investigated the pharmacological effects of Sema3A in chondrogenic differentiation. The amount of Sema3A secreted into the culture supernatant was measured using an enzyme-linked immunosorbent assay. The expression of chondrogenic differentiation-related factors, such as Type II collagen (COL2A1), Aggrecan (ACAN), hyaluronan synthase 2 (HAS2), SRY-box transcription factor 9 (Sox9), Runt-related transcription factor 2 (Runx2), and Type X collagen (COL10A1) in ATDC5 cells treated with Sema3A (1,10 and 100ng/mL) was examined using real-time reverse transcription polymerase chain reaction. Further, to assess the deposition of total glycosaminoglycans during chondrogenic differentiation, ATDC5 cells were stained with Alcian Blue. Moreover, the amount of hyaluronan in the culture supernatant was measured by enzyme-linked immunosorbent assay. The addition of Sema3A to cultured ATDC5 cells increased the expression of Sox9, Runx2, COL2A1, ACAN, HAS2, and COL10A1 during chondrogenic differentiation. Moreover, it enhanced total proteoglycan and hyaluronan synthesis. Further, Sema3A was upregulated in the early stages of chondrogenic differentiation, and its secretion decreased later. Sema3A increases extracellular matrix production and promotes chondrogenic differentiation. To the best of our knowledge, this is the first study to demonstrate the role of Sema3A on chondrogenic differentiation.

Gonadal Transcriptome Analysis Reveals that SOX17 and CYP26A1 are Involved in Sex Differentiation in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis).

The Chinese soft-shelled turtle (Pelodiscus sinensis) is an important aquaculture animal in China and exhibits growth dimorphism. Single-male cultures are often selected for higher economic efficiency. However, the mechanism of sex differentiation in P. sinensis is not well-known. In this study, a comparative transcriptome analysis of male (ZZ)- and 17β-oestradiol (E2)-induced pseudo-female (ZZ + E2)-stage embryonic gonads of P. sinensis was performed. A total of 420 differentially expressed genes (DEGs), which included 271 upregulated genes and 149 downregulated genes, were identified. These DEGs were mainly involved in several sex-related pathways, such as "ovarian steroidogenesis", "steroid hormone biosynthesis", "PPAR signalling pathway", and "metabolism of xenobiotics by cytochrome P450". In addition, 50 known and novel candidate genes involved in sex differentiation, such as the male-biased genes AMH, DMRT1, TBX1, and CYP26A1 and the female-biased genes CYP1A1, RASD1, and SOX17, were investigated and identified. For further verification, the full-length cDNAs of SOX17 and CYP26A1 were obtained. SOX17 contains a 1218-bp ORF and encodes 405 amino acids containing an HMG functional domain unique to the Sox superfamily. CYP26A1 contains a 1485-bp ORF and encodes 494 amino acids. Different expression levels of SOX17 and CYP26A1 could be detected in all the tested tissues of males and females. Notably, the expression of CYP26A1 was markedly greater in the gonads of male embryos (P < 0.05) than in those of female embryos, whereas the expression of SOX17 showed the opposite trend (P < 0.05). Taken together, the RNA-seq and qRT‒PCR results suggested potential roles for SOX17 and CYP26A1 in promoting female and male gonadal development, respectively, in P. sinensis. Our results provide new evidence for the mechanism of sex differentiation in P. sinensis.

Driving Mechanisms of Spatial Differentiation in Ecosystem Service Value in Opencast Coal Mines in Arid Areas: A Case Study in the Zhundong Economic and Technological Development Zone

The valuation of ecosystem services (ESs) is crucial for preserving ecosystems, assessing natural resources, and making decisions regarding compensation. In this study, we employed the InVEST model’s habitat quality (HQ) module to calculate the HQ and degradation levels in the study area using land use/land cover (LULC) data from 2000 to 2020. Our analysis utilized quantitative methods, including spatial correlation, hotspot analysis, and geo-probing, to determine the value of ESs and identify trends. Furthermore, we examined the spatial and temporal variation in the significance of ESs and their driving factors. The results show the following. (1) The primary LULC types in the Zhundong coalfield from 2000 to 2020 are grassland and barren areas. (2) The average value of the HQ index in the study area exhibited a generally decreasing trend. Between 2000 and 2010, HQ significantly declined, particularly in the region’s large barren industrial and mining zones. However, over time, the proportion of sites with minimal degradation improved steadily, resulting in better overall HQ in the study area by 2020. This pertains to the measures put in place by the local government to safeguard and rehabilitate the ecosystem. (3) The spatial distribution of the ecosystem service value (ESV) aligns with changes in HQ and LULC, with significant hotspots primarily observed in forest and grassland areas, nature reserves, and areas around water sources. (4) LULC, temperature, annual precipitation, and elevation are the main drivers of spatial variation in the ESV in the Zhundong area; the spatial variation in the ESV in the Zhundong coalfield is primarily influenced by the interaction between human factors and natural factors, in which LULC plays a dominant role. This study’s findings can guide the development of rational ecological planning, integrating resource conservation mining with effective zoning management.

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. Controlled laboratory study. BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. BMSCs labeled with 100 μg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. This study provides an alternative strategy for improving TBI healing after RCR.

Characterization of pore structures after ASP flooding for post-EOR

With the global assistance of oil fields entering the stage of improving oil recovery, diversified composite flooding technology has become one of the key research targets. This article takes composite flooding to improve oil recovery as the research object, explores the differential mechanism of crude oil displacement efficiency under water flooding and composite flooding conditions, and elucidates the dynamic evolution characteristics of pore structure before and after composite flooding. Results show that: (a) The permeability and porosity of Daqing oilfield cores have a good correlation. The porosity of cores after water driving and ternary composite driving mainly ranged from 23.6 % to 27.4 % and 22.8 %–26.8 %. The water-driving permeability mainly ranged from 168 × 10−3 μm2 to 2162 × 10−3 μm2. Ternary composite driving permeability mainly ranges from 302 × 10−3 μm2 to 2307 × 10−3 μm2. (b) Compared with water driving, quartz and clay minerals are corroded by alkali during ternary composite driving. (c) Under the condition of similar permeability, the average pore size of the core after ternary composite driving is smaller than the average pore size after water driving.

How does market-incentive environmental regulation affect enterprises green growth? The mediating role of R&D investment and innovation output

Manufacturing enterprises is a country's economic mainstay. However, their longtime extensive growth pattern of “high growth and high emission” has brought huge environment pollution and restricted sustainable development. Under the circumstance of carbon reduction and global green development, market-incentive environmental regulation (MER) has attracted the attention of scholars and become a kind of important methods of encouraging manufacturing enterprises green growth. Presently, two fairly distinct viewpoints of “Follow Cost” and “Porter Hypothesis” both have their own supportive research results, and the explanation for the role of MER is completely opposite. What's more, empirical research at the enterprise level is scarce. Therefore, this study makes a further analysis from the perspective of enterprises heterogeneous innovation ability. Guided by the classic theory of “Follow Cost” and “Porter Hypothesis”, this study aims to evaluate the applicable conditions of MER's environmental improvement effect, and testing the differential impact mechanism of MER on enterprise Green Total Factor Productivity (GTFP), enterprise Green Technological Change (GTC) and enterprise Green Efficiency Change (GEC). All these give theoretical and empirical supplementation for the rationality of related theories. This study examines the hypotheses and mechanism according to 1220 Chinese manufacturing listed companies data 2011–2020. The empirical results indicate that: (1) In short term, MER has a significant positive impact on GTC, and a significant negative impact on GTFP and GEC. (2) As innovation driven factors, both enterprise R&D investment and innovation output play the mediating role. (3) Heterogeneity analysis indicates that the impact mechanism varies depending on enterprise industry-type, location and digital level. Thus, policymakers should develop appropriate MER policies, and manufacturing enterprises should strengthen technological innovation to help achieve environmental sustainability and profit performance.

Investigation on spontaneous recombination mechanisms in GaN based laser diodes under low injection current

This study works on the spontaneous recombination mechanisms of GaN-based laser diodes (LDs) under low injection current by examining their power–current (P–I) curves and electroluminescence spectra. Our investigation focuses on the behavior of differential efficiency in LDs under low injection current, revealing that a competition between impurity-related yellow emissions and band-edge blue emissions leads to a change in total luminescence efficiency. Using both experimental and simulating methods, the yellow emission peak is primarily attributed to carrier recombination in deep-level defects located on the LD's p-side. A detailed explanation to the differential efficiency changing mechanism is beneficial to improve the GaN-based LD performance in future fabrication.

Spatial Identification and Distribution Pattern of the Complexity of Rural Poverty in China Using Multisource Spatial Data

Regional poverty is one of the most serious challenges facing the world today. Poverty, antipoverty, and poverty alleviation are the focus of the attention of scholars and the public. This paper takes China’s counties as the research unit, selects the influencing factors of poverty from natural and socio-economic factors, establishes an evaluation index system, simulates the natural poverty index and socio-economic poverty eradication index of each county, and clarifies the distribution characteristics of spatial poverty using GIS spatial analysis and BP artificial neural network. The results indicate that natural factors are the main cause of poverty in Chinese counties, with 710 counties having a high natural poverty index, accounting for nearly 30% of the total number of counties in the country. The national county-level natural poverty index shows a clear strip distribution pattern along latitude and longitude, with a strip distribution from north to south and from west to east; socio-economic factors have played a certain role in poverty alleviation, with as many as 1521 counties with low socio-economic poverty alleviation indices, accounting for approximately 64% of the total number of counties in the country. The spatial distribution of the county-level socio-economic poverty alleviation index is relatively fragmented. Through spatial scanning statistics, a total of 44 county poverty pressure index risk clusters reached a statistical significance level, involving 243 counties and districts. In poverty reduction practice, the internal counties and districts of contiguous poverty-stricken areas should strengthen cooperation and exchange. In the process of poverty alleviation and development, targeted poverty alleviation and economic development should be carried out based on the poverty-dominant type and self-development ability of the county, in order to improve efficiency. Regions that are relatively prosperous and have taken the lead in poverty reduction should play a leading and exemplary role in strengthening the radiation power of regional central cities. The prominent feature of this study is the comprehensive utilization of multisource data and the use of new spatial analysis methods (flexible spatial scanning method is widely used in the field of infectious disease prevention and control research). By constructing a multidimensional poverty measurement system that includes natural and social factors, it distinguishes the differences between the factors that cause poverty and the factors that eliminate poverty in regional poverty. At the same time, the flexible spatial scanning detection method was used to detect the differentiation mechanism of poverty spatial patterns.

Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation

HIV latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to-macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed protein kinase C signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing proinflammatory M1 macrophages suppressed HIV reactivation while anti-inflammatory M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive-oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and found that inhibitors of the thioredoxin (Trx) system acted as latency-promoting agents in T-cells and monocytes, but opposingly acted as latency-reversing agents in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.

Stratification and prognostic evaluation of breast cancer subtypes defined by obesity-associated genes

ObjectiveBreast cancer was the most common type of cancer among women worldwide, significantly impacting their quality of life and survival rates. And obesity has been widely accepted as an important risk factor for breast cancer. However, the specific mechanisms by which obesity affects breast cancer were still unclear. Therefore, studying the impact mechanisms of obesity as a risk factor for breast cancer was of utmost importance.MethodsThis study was based on TCGA breast cancer RNA transcriptomic data and the GeneCard obesity gene set. Through single and multiple factor Cox analysis and LASSO coefficient screening, seven hub genes were identified. The independent mechanisms of these seven hub genes were evaluated from various aspects, including survival data, genetic mutation data, single-cell sequencing data, and immune cell data. Additionally, the risk prognosis model and the neural network diagnostic model were established to further investigate these seven hub genes. In order to achieve precision treatment for breast cancer (BRCA), based on the RNA transcriptomic data of the seven genes, 1226 BRCA patients were divided into two subtypes: BRCA subtype 1 and BRCA subtype 2. By studying and comparing the immune microenvironment, investigating the mechanisms of differential gene expression, and exploring the mechanisms of subnetworks, we aim to explore the clinical differences in the presentation of BRCA subtypes and achieve precision treatment for BRCA. Finally, qRT-PCR experiments were conducted to validate the conclusions of the bioinformatics analysis.ResultsThe 7 hub genes showed good diagnostic independence and can serve as excellent biomarkers for molecular diagnosis. However, they do not perform well as independent prognostic molecular markers for BRCA patients. When predicting the survival of BRCA patients, their AUC values at 1 year, 3 years, and 5 years are mostly below 0.5. Nevertheless, through the establishment of the risk prognosis model considering the combined effect of the seven hub genes, it was found that the survival prediction of BRCA patients can be significantly improved. The risk prognosis model, compared to the independent use of the seven hub genes as prognostic markers, achieved higher timeROC AUC values at 1 year, 3 years, and 5 years, with values of 0.651, 0.669, and 0.641 respectively. Additionally, the neural network diagnostic model constructed from the 7 genes performs well in diagnosing BRCA, with an AUC value of 0.94, accurately identifying BRCA patients. The two subtypes identified by the seven hub genes exhibited significant differences in survival period, with subtype 1 having a poor prognosis. The differential mechanisms between the two subtypes mainly originate from regulatory differences in the immune microenvironment. Finally, the results of this study’s bioinformatics analysis were validated through qRT-PCR experiments.Conclusion7 hub genes serve as excellent independent biomarkers for molecular diagnosis, and the neural network diagnostic model can accurately distinguish BRCA patients. In addition, based on the expression levels of these seven genes in BRCA patients, two subtypes can be reliably identified: BRCA subtype 1 and BRCA subtype 2, and these two subtypes showed significant differences in BRCA patient survival prognosis, proportion of immune cells, and expression levels of immune cells. Among them, patients with subtype 1 of BRCA had a poor prognosis.

Direct load control-based optimal scheduling strategy for demand response of air-conditioning systems in rural building complex

The abrupt surge in electricity consumption for air-conditioning (AC) in rural areas has exacerbated the rural power supply and demand imbalance, presenting a significant challenge to the reliability and stability of power provision in rural low-voltage grids. Implementing power demand response (DR) in buildings is recognized as an effective solution to address the grid's power imbalance and reliability issues. Among various building DR strategies, direct load control (DLC) stands out as a proficient approach to rapidly curtail building AC loads. However, applying this method solely to individual rural buildings proves less effective in peak regulation (PR). To fully exploit the DR potential of AC systems in rural building complex, it is essential to scale up the application of DLC. Consequently, a DLC-based DR optimal scheduling strategy is proposed for rural building complex AC systems. This strategy aims to meet PR demand and maximize the benefits for load aggregator. It establishes four DLC methods and differential compensation mechanisms, taking into account the varying thermal comfort requirements of AC users. The DR optimization model is solved using a genetic algorithm (GA), with PR demand derived from long and short-term memory neural network predictions. To validate the proposed strategy, a simulation study is conducted on a 200-unit farmhouse AC system, utilizing a typical rural soil source heat pump system in Xi'an, Shaanxi Province. The results demonstrate that the strategy surpasses the PR target by approximately 6.65 % during the DR period, while ensuring a minimum level of thermal comfort for all user categories. Additionally, it yields a PR benefit of 88.73 yuan per day for all users, thereby promoting the adoption of clean energy in rural areas.

LncRNA in periodontal tissue-derived cells on osteogenic differentiation in the periodontitis field.

Periodontitis can lead to the destruction of periodontal tissues and potentially tooth loss. Numerous periodontal tissue-derived cells display osteogenic differentiation potential. The presence of differentially expressed long non-coding RNAs (lncRNAs) in these cells indicate their ability to regulate the process of osteogenic differentiation. We aim to elucidate the various lncRNA-mediated regulatory mechanisms in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis at epigenetic modification, transcriptional, and post-transcriptional levels. We systematically searched the PubMed, Web of Science, and ScienceDirect databases to identify relevant literature in the field of periodontitis discussing the role of lncRNAs in regulating osteogenic differentiation of periodontal tissue-derived cells. The identified literature was subsequently summarized for comprehensive review. In this review, we have comprehensively summarized the regulatory mechanisms of lncRNAs in the osteogenic differentiation of periodontal tissue-derived cells in the field of periodontitis and discussed how these lncRNAs provide novel perspectives for understanding the pathogenesis and progression of periodontitis. These results indicate the pivotal role of lncRNAs as regulators in the osteogenic differentiation of periodontal tissue-derived cells, providing a solid basis for future investigations on the role of lncRNAs in the periodontitis field.

Elucidating the Role of circTIAM1 in Guangling Large-Tailed Sheep Adipocyte Proliferation and Differentiation via the miR-485-3p/PLCB1 Pathway.

Fat tissue-a vital energy storage organ-is intricately regulated by various factors, including circular RNA, which plays a significant role in modulating fat development and lipid metabolism. Therefore, this study aims to clarify the regulatory mechanism of sheep adipocyte proliferation and differentiation by investigating the involvement of circTIAM1, miR-485-3p, and its target gene PLCB1. Through previous sequencing data, circTIAM1 was identified in sheep adipocytes, with its circularization mechanism elucidated, confirming its cytoplasmic localization. Experimental evidence from RNase R treatment and transcription inhibitors highlighted that circTIAM1 is more stable than linear RNA. Additionally, circTIAM1 promoted sheep adipocyte proliferation and differentiation. Furthermore, bioinformatic analysis demonstrated a robust interaction between miR-485-3p and circTIAM1. Further experiments revealed that miR-485-3p inhibits fat cell proliferation and differentiation by inhibiting PLCB1, with circTIAM1 alleviating the inhibitory effect via competitive binding. In summary, our findings elucidate the mechanism through which circTIAM1 regulates Guangling Large-Tailed sheep adipocyte proliferation and differentiation via the miR-485-3p-PLCB1 pathway, offering a novel perspective for further exploring fat metabolism regulation.

A Systematic Investigation into the Optimization of Reactive Power in Distribution Networks Using the Improved Sparrow Search Algorithm–Particle Swarm Optimization Algorithm

With the expansion of the scale of electric power, high-quality electrical energy remains a crucial aspect of power system management and operation. The generation of reactive power is the primary cause of the decline in electrical energy quality. Therefore, optimization of reactive power in the power system becomes particularly important. The primary objective of this article is to create a multi-objective reactive power optimization (MORPO) model for distribution networks. The model aims to minimize reactive power loss, reduce the overall compensation required for reactive power devices, and minimize the total sum of node voltage deviations. To tackle the MORPO problems for distribution networks, the improved sparrow search algorithm–particle swarm optimization (ISSA-PSO) algorithm is proposed. Specifically, two improvements are proposed in this paper. The first is to introduce a chaotic mapping mechanism to enhance the diversity of the population during initialization. The second is to introduce a three-stage differential evolution mechanism to improve the global exploration capability of the algorithm. The proposed algorithm is tested on the IEEE 33-node system and the practical 22-node system. The results indicate a reduction of 32.71% in network losses for the IEEE 33-node system after optimization, and the average voltage of the circuit increases from 0.9485 p.u. to 0.9748 p.u. At the same time, optimization results in a reduction of 44.07% in network losses for the practical 22-node system, and the average voltage of the circuit increases from 0.9838 p.u. to 0.9921 p.u. Therefore, the proposed method exhibits better performance for reducing network losses and enhancing voltage levels.

Differential deformation mechanism of E–W‐trending Weiningbeishan fold‐thrust belt from central Ningxia, NW China

The Weiningbeishan fold‐thrust belt (WFTB), located in the transitional zone of the Tibetan Plateau, Alxa Block and Ordos Basin, is an ancient intracontinental orogenic belt. In this article, structural analysis is conducted to more finely reveal differential deformation between the Devonian and Carboniferous strata in the WFTB. We found that the E–W‐trending open folds are mainly developed in the Upper Devonian Zhongning Formation (D3z), while the E–W‐trending close and tight folds are mainly developed in the Carboniferous strata. The N–S minimum shortening strain of the bottom boundary of Member 2 of the Upper Devonian Zhongning Formation (D3z2) is 21.1%, whereas the N–S minimum shortening strain of the bottom boundary of Member 2 of the Upper Carboniferous Danliangshan Formation (C2d2) is 64.1%. We propose that the E–W‐trending open folds in the Upper Devonian Zhongning Formation (D3z) and E–W‐trending close and tight folds in the Carboniferous strata were formed under the N–S compression during the Middle–Late Triassic. The Zhangyigou and Laoyagou faults are the main tear faults to accommodate differential displacement on the surface between the Upper Devonian Zhongning Formation (D3z) in the east and Carboniferous strata in the middle, which change into a décollement fault in the deep part of the Dafosigou fold area in the middle to accommodate differential deformation between the deep Upper Devonian Zhongning Formation (D3z) and Carboniferous strata. This study enables us to better understand the Mesozoic intracontinental deformation in response to far‐field plate‐boundary convergence in NW China.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.Graphical Downregulation of UHRF1 promotes the recovery of motor function in mice with spinal cord injury. By analyzing the RNA sequencing results of mice with spinal cord injury for 3 days and selecting UHRF1 for experimental validation, the study found that inhibiting UHRF1 can promote motor function recovery.

Garnet geochronology, major and trace element geochemistry of the Huanggangliang Fe-Sn polymetallic deposit, NE China

Cu-Fe (Au), W-Sn (Mo), Pb-Zn (Ag) and other element assemblages are common in many skarn deposits, but examples of Fe and Sn coexistence in nature are relatively rare. The Huanggangliang deposit in the southern Great Xing'an Range is the largest Fe-Sn polymetallic deposit in northern China, and there are five main mining areas (SK Ⅰ–SK Ⅴ) distributed along a SW–NE trend. SK Ⅰ and SK Ⅲ are the two larger mining areas in the Huanggangliang deposit, and their mineral assemblages and wall-rocks are significantly different: cassiterite and metal sulfides are duncommon in SK Ⅰ (andesite), while they are widely distributed in SK Ⅲ (marble). Garnet is widely distributed in SK Ⅰ and SK Ⅲ mining areas, and provides a good opportunity to explore the mechanism of Fe-Sn assemblage differentiation. Three types of garnet are distinguishable (Grt 1, Grt 2 and Grt 3) based on their mineral associations, textures and locations, and they mainly belong to the andradite-grossular solid solution series. The LA–ICP–MS U-Pb ages of the garnets from SK Ⅰ and SK Ⅲ are 136.0 ± 1.2 Ma (n = 25, MSWD = 1.9) and 136.2 ± 2.6 Ma (n = 37, MSWD = 1.8), respectively, suggesting that magmatic-hydrothermal activity in these two mining areas began at the same time. Grt 1 (located deep in SK Ⅰ and SK Ⅲ) and Grt 2 (located shallowly in SK Ⅰ) are mainly andradite, while Grt 3 (located shallowly in SK Ⅲ) is mainly grossular. They are all enriched in high field strength elements (HFSEs) and depleted in large ion lithophile elements (LILEs), and their REE patterns are enriched in light rare earth elements (LREEs) and depleted in heavy rare earth elements (HREEs). However, Grt Ⅰ-1a and 1b (deep garnets in SK Ⅰ) exhibit obvious positive Eu anomalies, while the other garnet types exhibit negative or no obvious Eu anomalies. Additionally, Grt 3 has high contents of V, Sn, U, Th, Zn and Y, and low contents of W and Mo. This pattern implies that the garnets in deep SK Ⅰ may have formed under oxidizing conditions with high temperatures, high oxygen fugacity (fO2) and weak acidity, while the garnets in shallow SK Ⅲ formed under reducing conditions with moderate temperatures, moderate fO2 and near-neutral pH. The garnets in shallow SK Ⅰ and deep SK Ⅲ may have formed under weak oxidation–reduction conditions at moderate to high temperatures, moderate fO2 and weakly acidic to neutral pH conditions. Our newly reported field geological, mineralogical, and geochemical data from garnet suggest that the ore-forming fluids of the Huanggangliang were magmatic-hydrothermal fluids mixed with slightly acidic external fluids, chloride complexes may have been the main transport ligands of REEs. The metallogenic environment may be an important factor leading to the difference of mineral assemblages in the Huanggangliang deposit.

Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells.

TIGIT is an inhibitory receptor on immune cells that outcompetes an activating receptor, CD226, for shared ligands. Tumor-infiltrating lymphocytes express TIGIT and CD226 on regulatory T cells (Treg) and on CD8+ T cells with tumor-reactive or exhausted phenotypes, supporting the potential of therapeutically targeting TIGIT to enhance anti-tumor immunity. To optimize the efficacy of therapeutic antibodies against TIGIT, it is necessary to understand whether there is therapeutic benefit from Fcγ receptor (FcγR) binding. Here, we showed that combining Fc-enabled (Fce) or Fc-silent (Fcs) anti-TIGIT with anti-PD-1 in mice resulted in enhanced control of tumors by differential mechanisms: Fce anti-TIGIT promoted depletion of intratumoral Treg, whereas Fcs anti-TIGIT did not. Despite leaving Treg numbers intact, Fcs anti-TIGIT potentiated activation of tumor-specific exhausted CD8+ populations in a lymph node-dependent manner. Fce anti-TIGIT induced antibody-dependent cell-mediated cytotoxicity against human Treg in vitro, and significant decreases in Treg were measured in the peripheral blood of Phase I solid tumor cancer patients treated with Fce anti-TIGIT. In contrast, Fcs anti-TIGIT did not deplete human Treg in vitro and was associated with anecdotal objective clinical responses in two Phase I solid tumor cancer patients in whom peripheral Treg frequencies remained stable on treatment. Collectively, these data provide evidence of pharmacological activity and anti-tumor efficacy of anti-TIGIT antibodies lacking the ability to engage FcγR.