Important Pathway Research Articles

Transcriptomic and metabolomic profiling reveals the drought tolerance mechanism of Illicium difengpi (Schisandraceae).

Illicium difengpi (Schisandraceae), an endangered medicinal plant endemic to karst areas, is highly tolerant to drought and thus can be used as an ideal material for investigating adaptive mechanism to drought stress. The understanding of the drought tolerance of I. difengpi, especially at the molecular level, is lacking. In the present study, we aimed to clarify the molecular mechanism underlying drought tolerance in endemic I. difengpi plant in karst regions. The response characteristics of transcripts and changes in metabolite abundance of I. difengpi subjected to drought and rehydration were analyzed, the genes and key metabolites responsive to drought and rehydration were screened, and some important biosynthetic and secondary metabolic pathways were identified. A total of 231,784 genes and 632 metabolites were obtained from transcriptome and metabolome analyses, and most of the physiological metabolism in drought-treated I. difengpi plants recovered after rehydration. There were more upregulated genes than downregulated genes under drought and rehydration treatments, and rehydration treatment induced stable expression of 65.25% of genes, indicating that rehydration alleviated drought stress to some extent. Drought and rehydration treatment generated flavonoids, phenolic acids, flavonols, amino acids and their derivatives, as well as metabolites such as saccharides and alcohols in the leaves of I. difengpi plants, which alleviated the injury caused by excessive reactive oxygen species. The integration of transcriptome and metabolome analyses showed that, under drought stress, I. difengpi increased glutathione, flavonoids, polyamines, soluble sugars and amino acids, contributing to cell osmotic potential and antioxidant activity. The results show that the high drought tolerance and recovery after rehydration are the reasons for the normal growth of I. difengpi in karst mountain areas.

Occurrence differences of hexachlorobutadiene and chlorobenzenes in road dust and roadside soil media in an industrial and residential mixed area in Eastern China

The road dust and roadside soil can act as both sinks and sources of hexachlorobutadiene (HCBD) and chlorobenzenes (CBzs), but comparative research on these two adjacent media is extremely limited. In this study, HCBD and CBzs were simultaneously analyzed in road dust and roadside soil samples from an area containing both industrial factories and residential communities in Eastern China. The road dust there was found to have 2–6 times higher contents of HCBD (mean 1.14 ng/g, maximum 6.44 ng/g) and ∑Cl3-Cl6CBzs (22.8 ng/g, 90.6 ng/g) than those in the roadside soil. The spatial distributions of HCBD and CBzs in road dusts were affected by various types of sources, showing no significant discrepancy among the sites. On the contrast, HCBD and CBzs contamination in roadside soils occurring near several factories were strongly correlated to their industrial point sources. Risk assessments showed, at current contamination levels in the road dust and roadside soil, HCBD and CBzs are not likely to induce carcinogenic or non-carcinogenic risks to residents in the studied area. Nevertheless, road dust ingestion, as the major exposure pathway of HCBD and CBzs, should be avoided to reduce the exposure risk. These findings based on the contamination differences between two media provide a new perspective and evidence for screening important sources and exposure pathway of HCBD and CBzs, which would be helpful to their source identification and risk control.

Differential Expression of Fibrinogen Alpha and Its Potential Involvement in Osteoarthritis Pathogenesis.

The deterioration of cartilage tissue and other joint components composed of synovial tissue is a defining characteristic ofosteoarthritis (OA) disease. Because of the lack of understanding of the underlying cause and important molecular pathways, there are currently no effective diagnostic or treatment methods for OA. The purpose of the study is to find a specific protein biomarker with high sensitivity and specificity in order to understand the pathophysiology of the disease and the underlying molecular pathways. We examined plasma samples of matched age and sex from OA patients (n = 150) and healthy controls (HC) (n = 70) to find proteins that were differentially expressed and validated by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence. The results of western blotting demonstrated that the expression level of the fibrinogen alpha (FGA) protein was higher in plasma samples of osteoarthritis (OAPL) (p = 0.0343), and the ROC (receiver operating characteristic curve) curve supported the high sensitivity (95.22%) and specificity (74%) of FGA in OA plasma compared to healthy controls. FGA protein was detected to be deposited in the synovial tissue of OA patients (p = 0.0073). By activating the Toll-like receptor (TLR-4) receptor pathway in PBMCs (p = 0.04) and synovial tissue, FGA protein may be involved in the molecular mechanism of OA pathogenesis. Our findings collectively suggested that FGA, which is significantly expressed in OA plasma, synovial tissue, and PBMCs and is connected to the disease's advancement through the TLR-4 receptor, may serve as a diagnostic or disease-evolving tool for OA.

Gene Expression Array Analyses Predict Proto-Oncogene Expression During Perineural Invasion in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma is the tumor type with the highest incidence of perineural invasion. This study tries to identify the differentially expressed genes regulated between pancreatic ductal adenocarcinoma tissues with perineural invasion and without perineural invasion. The GSE102238 profile was downloaded. Gene function and pathway analysis were subsequently conducted. A protein-protein interaction network was constructed to search for hub genes. Both univariate Cox analysis and multivariate Cox analysis were calculated to identify prognostic factors. Quantitative real-time polymerase chain reaction (RT-PCR) and overall survival analysis of hub genes were used to verify. Our study identified 242 differentially expressed genes including 68 upregulated differentially expressed genes and 174 downregulated differentially expressed genes, which were involved in important functions and pathways. Nine relevant core genes using protein-protein interaction analysis as well as nestin (NES)/vascular endothlial growth factor (VEGF) signaling pathway which is highly related to the pathological process of perineural invasion in pancreatic ductal adenocarcinoma were also discovered. The differentiation was identified as an independent prognostic factor (P < .05) after multivariate Cox analysis. Three upregulated genes (JUP, CALM1, and NES) and 6 downregulated genes (EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3) were validated by quantitative RT-PCR and they all had markedly worse overall survival (P < .05). This analysis showed that 9 core genes including JUP, CALM1, NES, EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3, as well as NES/VEGF signaling pathway, have a relationship with the development process of perineural invasion in pancreatic ductal adenocarcinoma. Cox analysis and overall survival analysis suggested differentiation as an independent prognostic factor and key roles for these 9 hub genes in perineural invasion prognosis in pancreatic ductal adenocarcinoma.

Characterizing 226Ra and its daughters in coastal zone groundwater of a typical human-activity affected bay: occurrence, safety, and source evaluation.

Due to their extremely toxic properties, 226Ra and it daughters (222Rn, 210Pb, and 210Po) in drinking groundwater require monitoring. Recent studies have reported exceptionally high levels of natural 210Po (up to 10,000Bq/m3), 226Ra, and 222Rn isotopes in groundwater. This study aims to provide background data on 226Ra and its daughter radionuclides in the typical agricultural-industrial Dongshan Bay (DSB) before the construction of Zhangzhou Nuclear Power Plant (Zhangzhou NPP). The measurement results indicate that no abnormally high activities of 210Po and 210Pb were detected in the investigated wells. Strong positive correlations between 210Pb and 210Po, as well as between 222Rn and 210Pb activities, suggest that the origins of 210Pb and 210Po in groundwater are strongly influenced by the decay of the parent radionuclides 222Rn and 210Pb, respectively. In the DSB coastal zone groundwater, significant deficiencies of 210Po relative to 210Pb and 210Pb relative to 222Rn were observed, providing further evidence that 210Po and 210Pb are also effectively scavenged due to their geochemical properties (specifically particle affinity) within the groundwater-aquifer system. A systematic comparison among all relevant water bodies in the DSB revealed that the activity concentrations of 210Pb and 210Po in groundwater were the highest, except for rainwater. Based on the evaluation of 210Pb sources, the results imply that submarine groundwater discharge (SGD) is an important pathway for transferring radionuclides (such as 210Pb) from land to the nearshore marine environment, even though the study area has a lower 210Pb background groundwater. By considering all the 210Pb's sources in the DSB, we found low 210Pb background groundwater discharge still needs to be taken into account for small-scale bays. This is because SGD was calculated to be one of the most important 210Pb sources in the bay during observation season. Regardless of whether the system is in a normal state or a nuclear accident emergency state, greater attention should be paid to the groundwater discharge of radionuclides into the ocean.

Exploration of natural processes and anthropogenic inputs by Zn isotopes in suspended particulate matter: A case study from the Lancang River in Southwest China

River is an important pathway for the biogeochemical cycle of Zn. This study reports Zn concentration and δ66Zn composition for suspended particulate matter (SPM) from Lancang River basin in Southwest China, and explore the impact of natural processes and human activities on Zn cycle. The SPM samples have a much higher average Zn content (162 mg kg−1) than that of the upper crust (67.0 mg kg−1), but it is close to the value of the Pearl River (187 mg kg−1). The enrichment factor (EF) values of Zn in SPM range from 1.08 to 6.88, with an average of 2.15, which does not show significant pollution characteristics. The δ66Zn values in SPM range from −0.67‰ to +0.63‰, with an average of +0.13‰. The δ66Zn values showed positive correlation with Ca/Mg ratios while showed little correlation with Zn contents in SPM. It indicated that anthropogenic sources have limited influence on SPM, and the Zn isotope composition in SPM is more likely to be inherited from the weathered rocks materials and influenced by natural fractionation processes in river water. This result contributes to understanding of the geochemical cycling process of Zn and its environmental effects in water.

The emergence of counter-urbanisation in China: Can it be a pathway for rural revitalisation?

China has also experienced a phenomenon of counter-urbanisation. Many urban residents have moved to suburban and even remote rural areas for living, establishing and operating businesses over the past decade. However, research is scarce on the counter-urbanisation trend in China. This paper investigates the driving forces behind the migration of China's high-and-middle-income groups to rural areas in the Yangtze River Delta region and their impacts on rural villagers and development. The paper contends that counter-urbanisation serves as an important pathway for rural revitalisation. More significantly, China's rural land ownership system facilitates the migration of urban dwellers to rural areas, thereby promoting rural revitalisation while avoiding the rural gentrification observed in Europe and the United States. In light of this, the authors propose a new term “Rural Middle-class Formation” as a Chinese type of “rural gentrification” to achieve common prosperity in both urban and rural areas and to distinguish it from “rural gentrification."

Nanomedicine for cancer targeted therapy with autophagy regulation.

Nanoparticles have unique physical and chemical properties and are currently widely used in disease diagnosis, drug delivery, and new drug development in biomedicine. In recent years, the role of nanomedical technology in cancer treatment has become increasingly obvious. Autophagy is a multi-step degradation process in cells and an important pathway for material and energy recovery. It is closely related to the occurrence and development of cancer. Because nanomaterials are highly targeted and biosafe, they can be used as carriers to deliver autophagy regulators; in addition to their favorable physicochemical properties, nanomaterials can be employed to carry autophagy inhibitors, reducing the breakdown of chemotherapy drugs by cancer cells and thereby enhancing the drug's efficacy. Furthermore, certain nanomaterials can induce autophagy, triggering oxidative stress-mediated autophagy enhancement and cell apoptosis, thus constraining the progression of cancer cells.There are various types of nanoparticles, including liposomes, micelles, polymers, metal-based materials, and carbon-based materials. The majority of clinically applicable drugs are liposomes, though other materials are currently undergoing continuous optimization. This review begins with the roles of autophagy in tumor treatment, and then focuses on the application of nanomaterials with autophagy-regulating functions in tumor treatment.

Enhanced Sulfate Formation from Gas-Phase SO2 Oxidation in Non–•OH–Radical Environments

Recent research on atmospheric particle formation has shown substantial discrepancies between observed and modeled atmospheric sulfate levels. This is because models mostly consider sulfate originating from SO2 oxidation by •OH radicals in mechanisms catalyzed by solar radiation while ignoring other pathways of non-radical SO2 oxidation that would substantially alter atmospheric sulfate levels. Herein, we use high-level quantum chemical calculations based on density functional theory and coupled cluster theory to show that monoethanolamine (MEA), a typical alkanolamine pollutant released from CO2 capture technology, can facilitate the conversion of atmospheric SO2 to sulfate in a non–•OH–radical oxidation mechanism. The initial process is the MEA-induced SO2 hydrolysis leading to the formation of HOSO2−•MEAH+. The latter entity is thereafter oxidized by ozone (O3) and nitrogen dioxide (NO2) to form HSO4−•MEAH+, which is an identified stabilizing entity in sulfate-based aerosol formation. Results show that the HOSO2−•MEAH+ reaction with O3 is kinetically and thermodynamically more feasible than the reaction with NO2. The presence of an additional water molecule further promotes the HOSO2−•MEAH+ reaction with O3, which occurs in a barrierless process, while it instead favors HONO formation in the reaction with NO2. The investigated pathway highlights the potential role alkanolamines may play in SO2 oxidation to sulfate, especially under conditions that are not favorable for •OH production, thereby providing an alternative sulfate source for aerosol modeling. The studied mechanism is not only relevant to sulfate formation and may effectively compete with reactions with sulfur dioxide and hydroxyl radicals under heavily polluted and highly humid conditions such as haze events, but also an important pathway in MEA removal processes.

Exploring the oxidative rancidity mechanism and changes in volatile flavors of watermelon seed kernels based on lipidomics

Watermelon seed kernels (WSK) are prone to oxidative rancidity, while their evaluation biomarkers and changes in volatile flavor are still unknown. The research tracked the changes in volatile compounds and lipid components before and after rancidity using HS-SPME-GC-O-MS and lipidomic techniques. The results showed the flavor of watermelon seed kernels changed significantly before and after rancidity, from mild aroma to rancidity. A total of 42 volatile compounds were detected via GC-O-MS, and a total of 220 lipid molecules were detected via lipidomic technology. 55 lipids with significant differences were screened via multivariate statistical analysis. Combining the above analysis, it found that glycerol phospholipid and glyceride pathways were the most important metabolic pathways and 1-Pentanol and styrene could be used as potential biomarkers to judge the rancidity process of watermelon seed kernels. The research could provide powerful technical support for the storage, transportation and freshness preservation of watermelon seed kernels.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing

BackgroundRotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients.MethodsRNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT.ResultsIn total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients.ConclusionsWe preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Identification and validation of iron metabolism genes in osteoporosis

BackgroundOsteoporosis is the most common metabolic bone disease in humans. Exploring the expression difference of iron metabolism-related genes in osteoporosis can provide a new target for diagnosis and treatment.MethodsFirst, we used online databases to identify differentially expressed genes (DEGs) related to iron metabolism in patients with osteoporosis. The differential genes were comprehensively analyzed by bioinformatics method (GO, KEGG, GSEA, immune infiltration analysis, PPI). The expression levels of hub genes and important signaling pathways were verified by qRT-PCR and Western blotting.ResultsA total of 23 iron metabolism-related genes with significant differences were identified, which were enriched in “regulation of protein dephosphorylation” and “negative regulation of protein dephosphorylation”. The GSEA results, heme metabolism and Myc targets v1 were among the top two pathways, both upregulated. The immune infiltration analysis revealed that the expressions of genes such as ABCA5, D2HGDH, GNAI2, and CTSW were correlated with the infiltration degree of significantly different cells. The PPI network contained 12 differentially expressed iron metabolism-related genes. Additionally, YWHAE, TGFB1, PPP1R15A, TOP2A, and CALR were mined as hub genes using the Cytoscape software. qRT PCR showed that the expression of TGF-β1, YWHAE, TOP2A and CALR increased. We also verified the expression of related proteins and genes in the oxidative stress signaling pathway by qRT PCR and Western blotting. The results showed that Mob1, YAP and TAZ molecules were highly expressed at the gene and protein levels.ConclusionsThese differentially expressed iron metabolism-related genes could provide new potential targets for the diagnosis and treatment of osteoporosis.

Targeting one-carbon metabolism for cancer immunotherapy.

One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients. We collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy. In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. Targeting one-carbon metabolism is useful for cancer immunotherapy.

Novel process for high value utilization of high-alumina fly ash: valuable metals recovery and mesoporous silica in situ preparation.

Extraction of valuable metals besides silica from high-alumina fly ash is one of the most important high-value utilization pathways. However, it is difficult to realize high-efficiency extraction due to the stable structure e.g. of quartz and mullite. In this paper, mineral phase transformation for valuable metal recovery and mesoporous silica in situ preparation from fly ash by a selective acid leaching method was proposed. The mineral phase transformation, dissolution behavior of each metal, and pore structure of fly ash derived mesoporous silica were systematically investigated. The results show that the co-activation of fly ash by Na2CO3-K2CO3 formed the phases of kalsilite and (Na, K)AlSiO4. During the acid leaching process, Al, Li, and Ga could be leached with the efficiencies of 86.17%, 89%, and 80% in the FK system. In the FN system, the efficiencies of Al, Li, and Ga are 92.38%, 95%, and 83%, respectively. The crystal plane (002) was destroyed for kaliophilite while all the crystal planes were destroyed for nepheline. With the increase of HCl solution concentration, the porous silica exhibited the same change order of pore shape. The pore structure of as-prepared porous silica was type IV and the hysteresis loop was type H3, and the specific surface areas could be 565.54, 448.02, and 746.76 m2 g-1, respectively. Finally, the leaching liquors can be used to produce crystal aluminum chloride, lithium carbonate and gallium. This paper might provide technical support for full recycling of high-value resources from fly ash.

Dynamics studies for the multi-well and multi-channel reaction of OH with C2H2 on a full-dimensional global potential energy surface.

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

Comparative Transcriptomics Data Profiling Reveals E2F Targets as an Important Biological Pathway Overexpressed in Intellectual Disability Disorder.

Intellectual disability (ID) is an early childhood neurodevelopmental disorder that is characterized by impaired intellectual functioning and adaptive behavior. It is one of the major concerns in the field of neurodevelopmental disorders across the globe. Diversified approaches have been put forward to overcome this problem. Among all these approaches, high throughput transcriptomic analysis has taken an important dimension. The identification of genes causing ID rapidly increased over the past 3 to 5 years owing to the use of sophisticated high throughput sequencing platforms. Early monitoring and preventions are much important for such disorder as their progression occurs during fetal development. This study is an attempt to identify differentially expressed genes (DEGs) and upregulated biological processes involved in development of ID patients through comparative analysis of available transcriptomics data. A total of 7 transcriptomic studies were retrieved from National Center for Biotechnology Information (NCBI) and were subjected to quality check and trimming prior to alignment. The normalization and differential expression analysis were carried out using DESeq2 and EdgeR packages of Rstudio to identify DEGs in ID. In progression of the study, functional enrichment analysis of the results obtained from both DESeq2 and EdgeR was done using gene set enrichment analysis (GSEA) tool to identify major upregulated biological processes involved in ID. Our findings concluded that monitoring the level of E2F targets, estrogen, and genes related to oxidative phosphorylation, DNA repair, and glycolysis during the developmental stage of an individual can help in the early detection of ID disorder.

Identification of the atmospheric water sources and pathways responsible for the East Asian summer monsoon rainfall

AbstractThe East Asian summer monsoon rainfall provides water security and socio‐economic benefit for over 20% of the global population. However, the sources of this rainfall and how it is carried to the East Asian landmass are still uncertain. To address this, atmospheric water sources and pathways associated with the East Asian summer rainfall are identified and quantified in this study using atmospheric water trajectories, calculated with a novel Lagrangian framework. Evaporated water from the East Asian landmass is found to be the major contributor to East Asian rainfall, amounting to local recycling. The results further indicated that the south Indian Ocean is a major non‐local source for rainfall over southern East Asia during June to August. The role of the south Indian Ocean as a source of atmospheric water is one of the major findings of the study and would help in better understanding and predicting the East Asian summer rainfall. Evaporated waters from the Pacific Ocean (particularly the far‐west Pacific Ocean) dominate the non‐local contribution to precipitation over northern East Asia during June to September and over southern East Asian rainfall during September. The spatial structure of the East Asian rainfall is reported to be determined by the atmospheric waters that are evaporated and transported from the non‐local sources. The role of the north Indian Ocean and the South Asian landmass as a source of water for East Asian precipitation is minimal and restricted to southern East Asia. The cross‐equatorial Somali jet and equatorial trade winds associated with the western North Pacific subtropical high are important pathways for East Asian precipitation sourced over the south Indian Ocean and the Pacific Ocean respectively. In contrast, minor roles are attributed to the Bay of Bengal as a source, and midlatitude westerlies as a transport pathway, for East Asian precipitation.

Innervation density and types of nerves in prostate cancer.

Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions.

Organo-organic interactions dominantly drive soil organic carbon accrual.

Organo-mineral interactions have been regarded as the primary mechanism for the stabilization of soil organic carbon (SOC) over decadal to millennial timescales, and the capacity for soil carbon (C) storage has commonly been assessed based on soil mineralogical attributes, particularly mineral surface availability. However, it remains contentious whether soil C sequestration is exclusively governed by mineral vacancies, making it challenging to accurately predict SOC dynamics. Here, through a 400-day incubation experiment using 13 C-labeled organic materials in two contrasting soils (i.e., Mollisol and Ultisol), we show that despite the unsaturation of mineral surfaces in both soils, the newly incorporated C predominantly adheres to "dirty" mineral surfaces coated with native organic matter (OM), demonstrating the crucial role of organo-organic interactions in exogenous C sequestration. Such interactions lead to multilayered C accumulation that is not constrained by mineral vacancies, a process distinct from direct organo-mineral contacts. The coverage of native OM by new C, representing the degree of organo-organic interactions, is noticeably larger in Ultisol (~14.2%) than in Mollisol (~5.8%), amounting to the net retention of exogenous C in Ultisol by 0.2-1.3 g kg-1 and in Mollisol by 0.1-1.0 g kg-1 . Additionally, organo-organic interactions are primarily mediated by polysaccharide-rich microbial necromass. Further evidence indicates that iron oxides can selectively preserve polysaccharide compounds, thereby promoting the organo-organic interactions. Overall, our findings provide direct empirical evidence for an overlooked but critically important pathway of C accumulation, challenging the prevailing "C saturation" concept that emphasizes the overriding role of mineral vacancies. It is estimated that, through organo-organic interactions, global Mollisols and Ultisols might sequester ~0.1-1.0 and ~0.3-1.7 Pg C per year, respectively, corresponding to the neutralization of ca. 0.5%-3.0% of soil C emissions or 5%-30% of fossil fuel combustion globally.

Tumor Promoting Effect of Long Non-Coding RNA RP11-556E13.1 and its Clinical Significance in Hepatocellular Carcinoma.

The aim of this study was to reveal the function of the long non-coding RNA (lncRNA) RP11-556E13.1 (RP11) and its clinical significance in hepatocellular carcinoma (HCC). LncRNA and mRNA expression profiling was performed using lncRNA and mRNA microarrays in HCC and adjacent tissues. Human tissue samples were analyzed by semiquantitative real-time polymerase chain reaction (sqRT-PCR) to evaluate the expression of RP11. Smart silencer RNA (siRNA) was used to knockdown the expression of RP11 in HCC cells. The function of RP11 was determined by some cell function experiments in HCC cells. Western blotting (WB) was performed to detect proteins that were presumably associated with these function changes. An Affymetrix Human HTA2.0 microarray was used to detect the underlying mechanism of RP11 in HCC. lncRNA RP11 was the most significantly upregulated lncRNA in HCC tissues compared with the adjacent tissues (p < 0.05, fold change = 20.24). The expression of RP11 was significantly higher in HCC tissues compared to adjacent tissues in 112 tissue pairs (p < 0.05). The higher the expression of RP11 in HCC tissues, the bigger the tumor size, the poorer the histological differentiation, and the lower the overall survival rate of the patients (all p < 0.05). After the knockdown of RP11, HCC cells displayed inhibited proliferation, increased apoptosis rate, and G1/S arrest. Moreover, the expression of cleaved PARP1 and cleaved caspase-3 was increased. GO enrichment and KEGG pathway enrichment analysis showed some important pathways that might be related to the knockdown of RP11 in HCC cells. lncRNA RP11 is an HCC-promoting gene and a potential prognostic predictor of HCC.