Postoperative adjuvant chemotherapy is important for improving long-term survival in patients with colorectal cancer liver metastases undergoing simultaneous resection.

BACKGROUND AND AIM: A growing number of studies have demonstrated that neoadjuvant chemotherapy can improve the prognosis of patients with resectable colorectal liver metastases (CRLM). However, the routine use of postoperative adjuvant chemotherapy (POAC) for patients with CRLM after simultaneous resection remains controversial. This retrospective study investigated the impact of POAC on outcomes in patients with CRLM who underwent simultaneous resection of colorectal cancer tumors and liver metastases using propensity score matching (PSM) analysis. METHODS: From January 2009 to November 2020, patients with CRLM who underwent simultaneous resection were retrospectively enrolled. The confounding factors and selection bias were adjusted by 2:1 PSM. Patients were stratified into the POAC and non-POAC groups. Kaplan-Meier curves were utilized to compare overall survival (OS) and progression-free survival (PFS) between the groups. Univariate and multivariate Cox regression analyses were used to identify independent clinicopathological factors before and after PSM analysis. The utility of the model was evaluated using receiver operating characteristic (ROC) and calibration curves after PSM analysis. RESULTS: In total, 478 patients with resectable CRLM were enrolled and assigned to the POAC (n = 212, 60.9%) or non-POAC group (n = 136, 39.1%). After 2:1 PSM, there was no significant bias between the groups. Kaplan-Meier survival analysis revealed a significant effect of POAC on OS (P < 0.001) but not PFS. Multivariate Cox regression analysis identified T stage (T3-T4), lymph node metastasis, radiofrequency ablation during surgery, operative time ≥ 325 min, and the receipt of postoperative adjuvant chemotherapy (hazard ratio = 0.447, 95% confidence interval = 0.312-0.638, P < 0.001) as independent prognostic factors for OS. The areas under the ROC curves for the nomogram model for predicting 1-, 3-, and 5-year survival were 0.653, 0.628, and 0.678, respectively. Subgroups analysis suggested that POAC can enhance OS in patients with resectable CRLM with either low (1-2, P < 0.001) or high clinical risk scores (3-5, P = 0.020). CONCLUSIONS: Overall, this study identified POAC as a prognostic factor to predict OS in patients with CRLM undergoing simultaneous resection.

Mechanistic Insights Into the Rhodium-Catalyzed C-H Alkenylation/Directing Group Migration and [3+2] Annulation: A DFT Study.

The mechanism of the rhodium-catalyzed C-H alkenylation/directing group migration and [3+2] annulation of N-aminocarbonylindoles with 1,3-diynes has been investigated with DFT calculations. On the basis of mechanistic studies, we mainly focus on the regioselectivity of 1,3-diyne inserting into the Rh-C bond and the N-aminocarbonyl directing group migration involved in the reactions. Our theoretical study uncovers that the directing group migration undergoes a stepwise ß-N elimination and isocyanate reinsertion process. As studied in this work, this finding is also applicable to other relevant reactions. Additionally, the role of Na+ versus Cs+ involved in the [3+2] cyclization reaction is also probed.

The application value of mean red blood cell volume and red blood cell volume distribution width combined with total serum bilirubin in the early screening of neonatal hemolytic disease.

BACKGROUND: The hemolytic nature of hemolytic disease of the newborn (HDN) is described as the abnormal destruction and decomposition of red blood cells, causing heterogeneous manifestations such as abnormal red blood cell volume and morphology. Mean corpuscular volume (MCV) and red blood cell volume distribution width (RDW) are commonly used parameters related to red blood cell volume. Total serum bilirubin (TSB) is routinely monitored among newborns. This study aims to explore the value of MCV and RDW, combined with TSB, to improve the efficiency of HDN diagnosis. METHODS: Three hundred eighty-eight children with HDN and 371 children with non-HDN pathological jaundice who were diagnosed and treated in the neonatal department of our hospital from January 2019 to December 2020 were included in the study. Clinical data collected include examination results of laboratory indicators, such as MCV, coefficient of variation of red blood cell volume distribution width (RDW-CV), standard deviation of red blood cell volume distribution width (RDW-SD), and TSB. The differences in the indicators between the two groups of children were retrospectively analyzed. RESULTS: 1) The detection rate of HDN in children in the early group was higher than that in the late group (P < 0.001). 2) The early-stage group had lower TSB levels and higher values of MCV, RDW-CV and RDW-SD (P < 0.001). Compared with the children in the non-HDN group, the indices in the HDN group were higher in the early stage (P < 0.001). 3) In the early stage, the TSB, MCV, RDW-CV, and RDW-SD were positively correlated with the diagnosis of HDN (P < 0.001). Early monitoring of TSB, MCV, RDW-CV and RDW-SD was valuable for HDN detection, the area under the curve (AUC) was 0.729, 0.637, 0.715, and 0.685, respectively (P < 0.001). 4) After a binary logistic analysis at TSB > 163.3 µmol/L, MCV > 96.35fL, and RDW-CV > 16.05%, the diagnosis rate of HDN increased (P < 0.001). The AUC of the HDN detected using the combined indicators was 0.841. CONCLUSION: At MCV > 96.35fL or RDW-CV > 16.05%, children with jaundice in three days of birth (especially children with TSB > 163.3 µmol/L) should be screened for HDN. A combination of TSB, MCV, and RDW-CV can improve the early detection rate of HDN, contribute to reduce the readmission rate and risk of hyperbilirubinemia.

Driving factors of soil organic carbon sequestration under straw returning across China's uplands.

Straw returning is suggested as a sustainable agricultural practice to promote soil organic carbon (SOC) sequestration, whose magnitude can be influenced by climatic, edaphic and agronomic factors simultaneously. However, the driving factors regulating straw returning-induced SOC increase in China's uplands remain uncertain. This study conducted a meta-analysis by collecting data from 238 trials at 85 field sites. The results showed that straw returning significantly increased SOC content by an average of 16.1% ± 1.5% with an average sequestration rate of 0.26 ± 0.02 g kg-1 yr-1. The improvement effects were significantly better in the northern China (NE-NW-N) than in the eastern and central (E-C). SOC increases were more pronounced in C-rich and alkaline soils, in cold and dry climates, and under larger amounts of straw-C and moderate nitrogen fertilizer inputs. Longer experimental period resulted in higher SOC increase rates but lower SOC sequestration rates. Furthermore, partial correlation analysis and structural equation modelling revealed that total straw-C input was the key driving factor of SOC increase rate whereas straw returning duration was the dominant limiting factor of SOC sequestration rate across China. Climate conditions were potential limiting factors of SOC increase rate in NE-NW-N and SOC sequestration rate in E-C. It was suggested that straw returning with large application amounts should be more strongly recommended in uplands in NE-NW-N especially in the straw applications at the beginning, from the perspective of SOC sequestration.

Spin Manipulation in a Metal-Organic Layer through Mechanical Exfoliation for Highly Selective CO2 Photoreduction.

Spin manipulation of transition-metal catalysts has great potential in mimicking enzyme electronic structures to improve activity and/or selectivity. However, it remains a great challenge to manipulate room-temperature spin state of catalytic centers. Herein, we report a mechanical exfoliation strategy to in situ induce partial spin crossover from high-spin (s=5/2) to low-spin (s=1/2) of the ferric center. Due to spin transition of catalytic center, mixed-spin catalyst exhibits a high CO yield of 19.7 mmol g-1 with selectivity of 91.6 %, much superior to that of high-spin bulk counterpart (50 % selectivity). Density functional theory calculations reveal that low-spin 3d-orbital electronic configuration performs a key function in promoting CO2 adsorption and reducing activation barrier. Hence, the spin manipulation highlights a new insight into designing highly efficient biomimetic catalysts via optimizing spin state.

A controllable staining colorimetric method based on carboxylated cellulose membranes for early-warning and semi-quantitative detection of aflatoxins in water.

The group specific assay of total aflatoxins (AFs) often requires specific antibodies. A controllable staining colorimetric method was proposed to determine AFs by exploiting controllable electrostatic-staining of carboxylated cellulose membranes (CCMs) with Hg2+-capped gold nanoparticles (AuNPs). Under electrostatic force, Hg2+ connects AuNPs and CCMs like a bridge, causing CCMs to be stained by AuNPs. The two adjacent carbonyl groups in the AF structure can chelate Hg2+. When AFs are present, Hg2+ and AFs will form complexes, which reduces the attachment of AuNPs on the CCMs. Therefore, the different degrees of electrostatic-staining of CCMs show different color changes. Based on this phenomenon, a naked-eye colorimetric detection assay of AFs was designed. The visual limit of detection (VLOD) reached 10 ppb, which makes it easily and effectively complete the early-warning and semi-quantitative detection of AFs. To our knowledge, this is the first method for colorimetric detection of AFs based on the controllable electrostatic-staining mechanism, which can be used for the determination of AFs in actual water samples such as beer and beverages. Besides, the colorimetric sensing method based on the controllable electrostatic-staining mechanism provides a novel methodology for early-warning and semi-quantitative detection of toxic and hazardous substances.

Electronic Spin Moment As a Catalytic Descriptor for Fe Single-Atom Catalysts Supported on C2N.

The electrocatalytic activity of transition-metal-based compounds is strongly related to the spin states. However, the underlying relationship connecting spin to catalytic activity remains unclear. Herein, we carried out density functional theory calculations on oxygen reduction reaction (ORR) catalyzed by Fe single-atom supported on C2N (C2N-Fe) to shed light on this relationship. It is found that the change of electronic spin moments of Fe and O2 due to molecular-catalyst adsorption scales with the amount of electron transfer from Fe to O2, which promotes the catalytic activity of C2N-Fe for driving ORR. The nearly linear relationship between the catalytic activity and spin moment variation suggests electronic spin moment as a promising catalytic descriptor for Fe single-atom based catalysts. Following the revealed relationship, the ORR barrier on C2N-Fe was tuned to be as low as 0.10 eV through judicious manipulation of spin states. These findings thus provide important insights into the relationship between catalytic activity and spin, leading to new strategies for designing transition metal single-atom catalysts.

Adsorption of Organic Molecules and Surfactants on Graphene: A Coarse-Grained Study.

The research studies on the adsorption of surfactants on graphene help us to know how to use surfactants to exfoliate graphene from graphite or functionalize the graphene surface. Among them, molecular dynamics (MD) simulation has been widely used to investigate the adsorption of organic molecules and surfactants on graphene. In particular, coarse-grained (CG) MD simulation greatly improves the computational efficiency by simplifying the complexity of the studied systems, allowing us to explore the structure and dynamics of complex systems on larger spatial scales and longer time scales. However, an accurate prediction of the adsorption of surfactants on graphene is required by optimizing the interaction between surfactants and graphene, which is often overlooked by some CG models. In this work, we found that an accurate prediction of the adsorption enthalpies of organic molecules on graphene can be achieved by optimizing the interactions between organic molecules and benzene. Meanwhile, we simulated the adsorption of a surfactant on single-layer and double-layer graphene nanosheets, respectively. Our results revealed that increasing the temperature would favor the interactions between hydrophilic groups of surfactants. In addition, we discovered that the surfactant prefers to be adsorbed on the inner surfaces of double-layer graphene compared with the outer surfaces, and this is owing to the dehydration in the middle of double-layer graphene, which is beneficial to the hydrophilic interactions between surfactant molecules inside the double-layer graphene.

Regulating Photocatalysis by Spin-State Manipulation of Cobalt in Covalent Organic Frameworks.

While catalysis is highly dependent on the electronic structure of the catalyst, the understanding of catalytic performance affected by electron spin regulation remains challenging and rare. Herein, we have developed a facile strategy to the manipulation of the cobalt spin state over covalent organic frameworks (COFs), COF-367-Co, by simply changing the oxidation state of Co centered in the porphyrin. Density functional theory (DFT) calculations together with experimental results confirm that CoII and CoIII are embedded in COF-367 with S = 1/2 and 0 spin ground states, respectively. Remarkably, photocatalytic CO2 reduction results indicate that COF-367-CoIII exhibits favorable activity and significantly enhanced selectivity to HCOOH, accordingly much reduced activity and selectivity to CO and CH4, in sharp contrast to COF-367-CoII. The results highlight that the spin-state transition of cobalt greatly regulates photocatalytic performance. Theoretical calculations further disclose that the presence of CoIII in COF-367-Co is preferable to the formation of HCOOH but detrimental to its further conversion, which clearly accounts for its distinctly different photocatalysis over COF-367-CoII. To the best of our knowledge, this is the first report on regulating photocatalysis by spin state manipulation in COFs.

Lidocaine inhibits melanoma cell proliferation by regulating ERK phosphorylation.

The melanoma is responsible for the majority of all skin cancer-related deaths worldwide. Evidence suggests that local anesthetics provide some benefit in the treatment of cancer via inhibition of cellular proliferation, invasion and migration. However, the potential antiproliferative effects of local anesthetics in the treatment of melanoma remain to be elucidated. In this study, we investigated the antiproliferative effects and underlying mechanism of the commonly used local anesthetic (lidocaine) on melanoma cells. A375 melanoma cells were treated by lidocaine or vemurafenib. Cell Counting Kit-8, histological staining, flow cytometric analysis, immunohistochemical staining, and Western blot analyses were carried out to test the effects of lidocaine and vemurafenib on A375 cells. BALB/C-nu/nu mice intraperitoneally injected with A375 cells were treated by lidocaine, and then tumor volume and weight were calculated. Lidocaine exhibited vemurafenib-like effects totally. Lidocaine inhibited A375 melanoma cell proliferation in a dose- and time-dependent manner and colony formation also showed a dose-dependent inhibition. Lidocaine treatment resulted in the arrest of cell-cycle progression in the G1 phase and inhibited Ki-67 expression in a dose-dependent manner. This effect was associated with inhibited extracellular signal-regulated kinase (ERK) phosphorylation. In vivo experiments revealed that intravenous injections of lidocaine suppressed tumor volume and weight. Lidocaine inhibits melanoma cell proliferation in a dose- and time-dependent manner via a mechanism that may involve inhibition of the ERK signaling pathway. Thus, lidocaine may provide some benefit for the treatment of melanoma.

Responses of Active Ammonia Oxidizers and Nitrification Activity in Eutrophic Lake Sediments to Nitrogen and Temperature.

Ammonium concentrations and temperature drive the activities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB), but their effects on these microbes in eutrophic freshwater sediments are unclear. In this study, surface sediments collected from areas of Taihu Lake (China) with different degrees of eutrophication were incubated under three levels of nitrogen input and temperature, and the autotrophic growth of ammonia oxidizers was assessed using 13C-labeled DNA-based stable-isotope probing (SIP), while communities were characterized using MiSeq sequencing and phylogenetic analysis of 16S rRNA genes. Nitrification rates in sediment microcosms were positively correlated with nitrogen inputs, but there was no marked association with temperature. Incubation of SIP microcosms indicated that AOA and AOB amoA genes were labeled by 13C at 20°C and 30°C in the slightly eutrophic sediment, and AOB amoA genes were labeled to a much greater extent than AOA amoA genes in the moderately eutrophic sediment after 56 days. Phylogenetic analysis of 13C-labeled 16S rRNA genes revealed that the active AOA were mainly affiliated with the Nitrosopumilus cluster, with the Nitrososphaera cluster dominating in the slightly eutrophic sediment at 30°C with low ammonium input (1 mM). Active AOB communities were more sensitive to nitrogen input and temperature than were AOA communities, and they were exclusively dominated by the Nitrosomonas cluster, which tended to be associated with Nitrosomonadaceae-like lineages. Nitrosomonas sp. strain Is79A3 tended to dominate the moderately eutrophic sediment at 10°C with greater ammonium input (2.86 mM). The relative abundance responses of the major active communities to nitrogen input and temperature gradients varied, indicating niche differentiation and differences in the physiological metabolism of ammonia oxidizers that are yet to be described.IMPORTANCE Both archaea and bacteria contribute to ammonia oxidation, which plays a central role in the global cycling of nitrogen and is important for reducing eutrophication in freshwater environments. The abundance and activities of ammonia-oxidizing archaea and bacteria in eutrophic limnic sediments vary with different ammonium concentrations or with seasonal shifts, and how the two factors affect nitrification activity, microbial roles, and active groups in different eutrophic sediments is unclear. The significance of our research is in identifying the archaeal and bacterial responses to anthropogenic activity and climate change, which will greatly enhance our understanding of the physiological metabolic differences of ammonia oxidizers.

CO oxidation on Ru-Pt bimetallic nanoclusters supported on TiO2(101): The effect of charge polarization.

Pt-based catalyst is widely used in CO oxidation, while its catalytic activity is often undermined because of the CO poisoning effect. Here, using density functional theory, we propose the use of a Ru-Pt bimetallic cluster supported on TiO2 for CO oxidation, to achieve both high activity and low CO poisoning effect. Excellent catalytic activity is obtained in a Ru1Pt7/TiO2(101) system, which is ascribed to strong electric fields induced by charge polarization between one Ru atom and its neighboring Pt atoms. Because of its lower electronegativity, the Ru atom donates electrons to neighboring Pt. This induces strong electric fields around the top-layered Ru, substantially promoting the adsorption of O2/CO + O2 and eliminating the CO poisoning effect. In addition, the charge polarization also drives the d-band center of the Ru1Pt7 cluster to up-shift to the Fermi level. For surface O2 activation/CO oxidation, the strong electric field and d-band center close to the Fermi level can promote the adsorption of O2 and CO as well as reduce the reaction barrier of the rate-determining step. Meanwhile, since O2 easily dissociates on Ru1Pt7/TiO2(101) resulting in unwanted oxidation of Ru and Pt, a CO-rich condition is necessary to protect the catalyst at high temperature.

Bacterial Bioreporter-Based Mercury and Phenanthrene Assessment in Yangtze River Delta Soils of China.

Genetically engineered bacterial whole-cell bioreporters were deployed to investigate bioavailable mercury (b-Hg) and phenanthrene (b-PHE). Characterized by high sensitivity and specificity in aqueous solutions, the bioreporter system could detect in amended soils the concentrations of b-Hg and b-PHE in the ranges of 19.6 to 111.6 and 21.5 to 110.9 µg kg, respectively. The sensitivity of the system allowed for the combined analysis of b-Hg and b-PHE from real environmental samples. Therefore, soil samples from three large refinery facilities were tested, and the results from the instrumental analysis strongly correlated with the ones obtained with the bioreporter method. Large-scale and fast screening of soil contamination across the Yangtze River Delta in Eastern China was conducted. More than 36% of the samples contained b-Hg, whereas the fractions of b-PHE were below the detection limit for all the samples. These results indicated a higher toxicity and more hazardous condition for Hg contamination than for PHE. Population densities and airborne 10-µm particulate matter (PM10) concentrations were used as parameters for comparison with the spatial distribution of the b-Hg and b-PHE fractions. The results revealed that the bioreporters could offer a rapid and cost-efficient method to test soil samples from contaminated areas and provide a screening tool for environmental risk assessment.

Highly Active Graphene Oxide-Supported Cobalt Single-Ion Catalyst for Chemiluminescence Reaction.

Graphene- or graphene oxide (GO)-supported metallic nanoparticles and single metal atom as potentially effective catalysts for chemical reactions have recently received extensive research interests. However, metal utilization in nanoparticle catalysts is limited and metal atoms readily drift on the graphene surface and consequently form aggregated large particles, making practical applications limited. Here, we report metal ions directly immobilized on GO as a novel GO-supported single-ion catalyst for chemiluminecence (CL) reactions. It is found that GO-supported cobalt ions with good stability could catalyze strongly luminol-H2O2 and lucigenin-H2O2 CL reactions, accompanied by dramatically enhanced CL emission. Theoretical studies reveal that the coupling between Co2+ and GO induces effective polarization charges, improving chemical activity of the reaction site, which promotes the generation of intermediate radicals and accelerates the CL reactions. This work may be generalized to other GO-supported metal ions as catalysts for a wide range of chemical reactions. The developed GO-supported cobalt single-ion nanocomposites as nanointerfaces may find future applications in CL bioassays.

The O, OH and OOH-assisted selective coupling of methanol on Au-Ag(111).

Using density functional theory (DFT) calculations, we performed a thorough theoretical investigation on the catalytic mechanism of oxidative self-coupling of methanol with molecular oxygen on Au-Ag catalysts. It is found that molecular oxygen can be activated via a hydroperoxyl (OOH) intermediate by taking a hydrogen atom from co-adsorbed methanol with an energy barrier of 0.51 eV, which is actually the rate determining step for the overall reaction. The O, OH and OOH oxidant formation proceeds via two channels of I and II with low barriers. We demonstrated that the oxidative coupling of methanol by OOH, atomic oxygen, and hydroxyl is much more favorable than the total oxidation of methanol, and is responsible for the high selectivity of Au-Ag catalysts in methanol oxidation. The revealed activation mechanism provides an efficient pathway for optimizing the selective coupling of methanol with dioxygen.

Application of genetically engineered microbial whole-cell biosensors for combined chemosensing.

The progress of genetically engineered microbial whole-cell biosensors for chemosensing and monitoring has been developed in the last 20 years. Those biosensors respond to target chemicals and produce output signals, which offer a simple and alternative way of assessment approaches. As actual pollution caused by human activities usually contains a combination of different chemical substances, how to employ those biosensors to accurately detect real contaminant samples and evaluate biological effects of the combined chemicals has become a realistic object of environmental researches. In this review, we outlined different types of the recent method of genetically engineered microbial whole-cell biosensors for combined chemical evaluation, epitomized their detection performance, threshold, specificity, and application progress that have been achieved up to now. We also discussed the applicability and limitations of this biosensor technology and analyzed the optimum conditions for their environmental assessment in a combined way.

[Characterization of a novel electrogenic Clostridium sporogenes isolated from forest soil].

Objective: To identify and characterize an electrogenic bacterium SE6 isolated form forest soil. Methods: Pure culture of the strain was obtained by anaerobic incubation. It was identified based on morphology, physiology and biochemistry, and 16S rRNA gene sequencing analysis. The strain was inoculated in a dual chamber microbial fuel cell with LB medium as anolyte and potassium ferricyanide as catholyte, to characterize its electrogenic ability. Electrochemical impedance spectroscopy was conducted to analyze internal resistances of the MFCs. Extracellular electron transfer mechanism of the strain was explored by cyclic voltammetry. Biofilm on the anode surface was observed using scanning electron microscope. Results: The 16S rRNA gene sequence of strain SE6 was 100% phylogenetically related to Clostridium sporogenes. Their morphological, physiological and biochemical characteristics were identical. The maximum power density of the MFCs inoculated with SE6 was 44.42 mW/m2. The anodic resistance, cathodic resistance and ohmic resistance were (1488±193) Ω/cm2, (0.92±0.01) Ω/cm2 and (20.69±1.76) Ω/cm2, respectively. Cyclic voltammograms indicated the existence of an electrochemically active substance, of which the peak currents were linearly correlated with the scanning rates. The 1 µm-rodshaped bacteria densely attaching to the anode surface were observed in scanning electron micrographs. Conclusion: A novel electrogenic strain of C. sporogenes was isolated from forest soil, which transfers electrons extracellularly to electrode with high resistance.

The Rational Design of Atomically Dispersed Catalysts via Spin Manipulation.

The catalytic activity of transition-metal-based atomically dispersed catalysts is closely related to the spin states. Manipulating the spin state of metal active centers could directly adjust the d orbital occupancy and optimize the adsorption behavior and electron transfer of the intermediates and transition metals, which would enhance the catalytic activity. We summarize the means of manipulating spin states and the spin-related catalytic descriptors. In future work, we will build a quantifiable and accurate prediction intelligent model through artificial intelligence (AI) and machine learning tools. Furthermore, we will develop new spin regulation methods to carry out the directional regulation of atomically dispersed catalysts through this model, providing new insight into the rational design of transition-metal-based atomically dispersed catalysts through spin manipulation.

Fibroblast growth factor 21 alleviates unilateral ureteral obstruction-induced renal fibrosis by inhibiting Wnt/ß-catenin signaling pathway.

Fibroblast growth factor 21 (FGF21) is a key regulator of energy metabolism. Recent studies suggested that serum FGF21 levels increase with declining renal function. However, the link between FGF21 and kidney diseases and the direct effect of FGF21 in renal fibrosis remains unclear. In this study, FGF21 was upregulated in unilateral ureteral obstruction (UUO)-induced renal fibrosis and cellular fibrosis induced by transforming growth factor-ß, and renal expression of FGF21 was positively correlated with fibrosis markers. Additionally, FGF21 was regulated by Wnt/ß-catenin signaling pathway. The knockdown and overexpression of FGF21 in mouse tubular epithelial cells demonstrated that FGF21 alleviates renal fibrosis by inhibiting the Wnt/ß-catenin signaling pathway. To investigate the effect of FGF21 on renal fibrosis in vivo, we established an overexpression model by injecting the plasmid in mice and found that FGF21 overexpression relieved UUO-induced renal fibrosis and renal inflammatory response. Taken together, FGF21 is upregulated with the activation of Wnt/ß-catenin signaling pathway and alleviates renal fibrosis by inhibiting the activation of Wnt/ß-catenin signaling pathway in a negative feedback mode. These results provide a new understanding for the source of elevated serum FGF21 in patients with chronic kidney disease and prove that FGF21 is a direct inhibitor of the progression of renal fibrosis, thus providing novel therapeutic intervention insights for renal fibrosis.

Spatial transcriptomics in pancreatic cancer: advances, prospects and challenges.

Pancreatic cancer remains one of the deadliest malignancies with an overall 5-year survival rate of 13%. This dismal fact can be partly attributed to currently limited understanding of tumor heterogeneity and immune microenvironment. Traditional bulk-sequencing techniques overlook the diversity of tumor cells, while single-cell sequencing disorganizes the position localizing of cells in tumor microenvironment. The advent of spatial transcriptomics (ST) presents a novel solution by integrating location and whole transcript expression information. This technology allows for detailed observation of spatio-temporal changes across various cell subtypes within the pancreatic tumor microenvironment, providing insights into their potential functions. This review offers an overview of recent studies implementing ST in pancreatic cancer research, highlighting its instrumental role in investigating the heterogeneity and functions of tumor cells, stromal cells, and immune cells. On the basis, we also prospected and summarized the clinical application scenarios, technical limitations and challenges of ST technology in pancreatic cancer.