TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway in mice.

The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2-/- mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2-/- BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-ß1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.

Immobilization of Pb(II) by Bacillus megaterium-based microbial-induced phosphate precipitation (MIPP) considering bacterial phosphorolysis ability and Ca-mediated alleviation of lead toxicity.

Inappropriate handling of lead (Pb)-containing wastewater that is produced as a result of smelting activities threatens the surrounding environment and human health. The microbial-induced phosphate precipitation (MIPP) technology was applied to immobilize Pb2+ in an aqueous solution considering bacterial phosphorolysis ability and Ca-mediated alleviation of lead toxicity. Pb immobilization was accompanied by sample characterization in order to explore the inherent mechanism that affected the immobilization efficiency. Results showed that Ca2+ use elevated the immobilization efficiency through the prevention of bacterial physisorption and chemisorption, an enhancement to the phosphatase activity and the degree of SGP hydrolysis, and the provision of nucleation sites for Pb2+ to attach. The formation of the Pb-GP complex helped the bacteria to maintain its activity at the commencement of catalyzing SGP hydrolysis. The nucleated minerals that were precipitated in a columnar shape through a directional stacking manner under MIPP featured higher chemical stability compared to non-nucleated minerals. As a result, there were three pathways, namely, bacterial physisorption, bacterial chemisorption, and substrate chelation, applied for Pb immobilization. The immobilization efficiency of 99.6% is achieved by precipitating bioprecipitates including Pb5(PO4)3Cl, Pb10(PO4)6Cl2, and Ca2Pb3(PO4)3Cl. The findings accentuate the potential of applying the MIPP technology to Pb-containing wastewater remediation.

Struvite and ethylenediaminedisuccinic acid (EDDS) enhance electrokinetic-biological permeable reactive barrier removal of copper and lead from contaminated loess.

Removal of heavy metals using the electrokinetic (EK) remediation technology is restricted by soils containing a fraction of clay particles above 12%. Furthermore, it is also affected by hydroxide precipitation (focusing phenomenon) close to the cathode. A modified EK reactor containing a permeable reactive barrier (PRB) was proposed herein where the enzyme-induced carbonate precipitation (EICP) treatment was incorporated into the PRB. Despite that, NH4+-N pollution induced by the urea hydrolysis resulting from the EICP treatment causes serious threats to surrounding environments and human health. There were four types of tests applied to the present work, including CP, TS1, TS2, and TS3 tests. CP test neglected the bio-PRB, while TS1 test considered the bio-PRB. TS2 test based on TS1 test tackled NH4+-N pollution using the struvite precipitation technology. TS3 test based on TS2 test applied EDDS to enhance the removal of Cu and Pb. In CP test, the removal efficiency applied to Cu and Pb removals was as low as approximately 10%, presumably due to the focusing phenomenon. The removal efficiency was elevated to approximately 24% when the bio-PRB and the electrolyte reservoir were involved in TS1 test. TS2 test indicated that the rate of struvite precipitation was 40 times faster than the ureolysis rate, meaning that the struvite precipitate had sequestered NH4+ before it started threatening surrounding environments. The chelation between Cu2+ and EDDS took place when EDDS played a part in TS3 test. It made Cu2+ negatively surface charged by transforming Cu2+ into EDDSCu2-. The chelation caused those left in S4 and S4 to migrate toward the bio-PRB, whereas it also caused those left in S1 and S2 to migrate toward the anode. Due to this reason, the fraction of Cu2+ removed by the bio-PRB and the electrolyte reservoir is raised to 32% and 26% respectively, and the fraction of remaining Cu was reduced to 41%. Also, the removal efficiency applied to Pb removal was raised to 50%. Results demonstrate the potential of struvite and EDDS-assisted EK-PRB technology as a cleanup method for Cu- and Pb-contaminated loess.

Deterioration phenomenon of Pb-contaminated aqueous solution remediation and enhancement mechanism of nano-hydroxyapatite-assisted biomineralization.

Modern metallurgical and smelting activities discharge the lead-containing wastewater, causing serious threats to human health. Bacteria and urease applied to microbial-induced carbonate precipitation (MICP) and enzyme-induced carbonate precipitation (EICP) are denatured under high Pb2+ concentration. The nano-hydroxyapatite (nHAP)-assisted biomineralization technology was applied in this study for Pb immobilization. Results showed that the extracellular polymers and cell membranes failed to secure the urease activity when subjected to 60 mM Pb2+. The immobilization efficiency dropped to below 50% under MICP, whereas it due to a lack of extracellular polymers and cell membranes dropped to below 30% under EICP. nHAP prevented the attachment of Pb2+ either through competing with bacteria and urease or promoting Ca2+/Pb2+ ion exchange. Furthermore, CO32- from ureolysis replaced the hydroxyl (-OH) in hydroxylpyromorphite to encourage the formation of carbonate-bearing hydroxylpyromorphite of higher stability (Pb10(PO4)6CO3). Moreover, nHAP application overcame an inability to provide nucleation sites by urease. As a result, the immobilization efficiency, when subjected to 60 mM Pb2+, elevated to above 80% under MICP-nHAP and to some 70% under EICP-nHAP. The findings highlight the potential of applying the nHAP-assisted biomineralization technology to Pb-containing water bodies remediation.

Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines.

Electrophilic small molecules with novel reactivity are powerful tools that enable activity-based protein profiling and covalent inhibitor discovery. Here, we report a reactive heterocyclic scaffold, 4-chloro-pyrazolopyridine (CPzP) for selective modification of proteins via a nucleophilic aromatic substitution (SNAr) mechanism. Chemoproteomic profiling reveals that CPzPs engage cysteines within functionally diverse protein sites including ribosomal protein S5 (RPS5), inosine monophosphate dehydrogenase 2 (IMPDH2), and heat shock protein 60 (HSP60). Through the optimization of appended recognition elements, we demonstrate the utility of CPzP for covalent inhibition of prolyl endopeptidase (PREP) by targeting a noncatalytic active-site cysteine. This study suggests that the proteome reactivity of CPzPs can be modulated by both electronic and steric features of the ring system, providing a new tunable electrophile for applications in chemoproteomics and covalent inhibitor design.

Exploring DNA Damage and Repair Mechanisms: A Review with Computational Insights.

DNA damage is a critical factor contributing to genetic alterations, directly affecting human health, including developing diseases such as cancer and age-related disorders. DNA repair mechanisms play a pivotal role in safeguarding genetic integrity and preventing the onset of these ailments. Over the past decade, substantial progress and pivotal discoveries have been achieved in DNA damage and repair. This comprehensive review paper consolidates research efforts, focusing on DNA repair mechanisms, computational research methods, and associated databases. Our work is a valuable resource for scientists and researchers engaged in computational DNA research, offering the latest insights into DNA-related proteins, diseases, and cutting-edge methodologies. The review addresses key questions, including the major types of DNA damage, common DNA repair mechanisms, the availability of reliable databases for DNA damage and associated diseases, and the predominant computational research methods for enzymes involved in DNA damage and repair.

Metabolism-related signalling pathways involved in the pathogenesis and development of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) which formerly known as non-alcoholic fatty liver disease (NAFLD) is one of the causes of liver cirrhosis. Currently, a growing number of liver cirrhosis cases develop on the basis of MASLD, and the pathogenesis of MASLD remains unclear. This paper reviews the research progress on the involvement of different metabolism-related signalling pathways in the pathogenesis and development of MASLD.

Biopolymer-assisted enzyme-induced carbonate precipitation for immobilizing Cu ions in aqueous solution and loess.

Wastewater, discharged in copper (Cu) mining and smelting, usually contains a large amount of Cu2+. Immobilizing Cu2+ in aqueous solution and soils is deemed crucial in preventing its migration into surrounding environments. In recent years, the enzyme-induced carbonate precipitation (EICP) has been widely applied to Cu immobilization. However, the effect of Cu2+ toxicity denatures and even inactivates the urease. In the present work, the biopolymer-assisted EICP technology was proposed. The inherent mechanism affecting Cu immobilization was explored through a series of test tube experiments and soil column tests. Results indicated that 4 g/L chitosan may not correspond to a higher immobilization efficiency because it depends as well on surrounding pH conditions. The use of Ca2+ not only played a role in further protecting urease and regulating the environmental pH but also reduced the potential for Cu2+ to migrate into nearby environments when malachite and azurite minerals are wrapped by calcite minerals. The species of carbonate precipitation that are recognized in the numerical simulation and microscopic analysis supported the above claim. On the other hand, UC1 (urease and chitosan colloid) and UC2 (urea and calcium source) grouting reduced the effect of Cu2+ toxicity by transforming the exchangeable state-Cu into the carbonate combination state-Cu. The side effect, induced by 4 g/L chitosan, promoted the copper-ammonia complex formation in the shallow ground, while the acidic environments in the deep ground prevented Cu2+ from coordinating with soil minerals. These badly degraded the immobilization efficiency. The Raman spectroscopy and XRD test results tallied with the above results. The findings shed light on the potential of applying the biopolymer-assisted EICP technology to immobilizing Cu ions in water bodies and sites.

Applying the first microcapsule-based self-healing microbial-induced calcium carbonate materials to prevent the migration of Pb ions.

Lead (Pb) accumulation can lead to serious threats to surrounding environments and damage to the liver and kidneys. In the past few years, microbial-induced carbonate precipitation (MICP) technology has been widely applied to achieve Pb immobilization due to its environmentally friendly nature. However, harsh pH conditions can cause the instability of the carbonate precipitation to degrade or dissolve, increasing the potential of Pb2+ migration into nearby environments. In this study, microcapsule-based self-healing microbial-induced calcium carbonate (MICC) materials were applied to prevent Pb migration. The highest sporulation rate of 95.8% was attained at 7 g/L yeast extract, 10 g/L NH4Cl, and 3.6 g/L Mn2+. In the germination phase, the microcapsule not only prevented the bacterial spores from being threatened by the acid treatment but secured their growth and reproduction. Micro analysis also revealed that cerussite, calcite, and aragonite minerals were present, while extracellular polymeric substances (EPSs) were identified via Fourier transform infrared spectroscopy (FTIR). These results confirm their involvement in combining Pb2+ and Ca2+. The immobilization efficiency of above 90% applied to MICC materials was attained, while it of below 5% applied to no MICC use was attained. The findings explore the potential of applying microcapsule-based self-healing MICC materials to prevent Pb ion migration when the calcium carbonate degrades under harsh pH conditions.

Study on Cu- and Pb-contaminated loess remediation using electrokinetic technology coupled with biological permeable reactive barrier.

Although the electrokinetic (EK) remediation has drawn great attention because of its good maneuverability, the focusing phenomenon near the cathode and low removal efficiency remain to be addressed. In this study, a novel EK reactor was proposed to remediate Cu and Pb contaminated loess where a biological permeable reactive barrier (bio-PRB) was deployed to the middle of the EK reactor. For comparison, three test configurations, namely, CG, TG-1, and TG-2, were available. CG considered the multiple enzyme-induced carbonate precipitation (EICP) treatments, while TG-1 considered both the multiple EICP treatments and pH regulation. TG-2 further considered NH4+ recovery based on TG-1. CG not only improved Cu and Pb removals by the bio-PRB but also depressed the focusing phenomenon. TG-1 causes more Cu2+ and Pb2+ to migrate toward the bio-PRB and aggravates Cu and Pb removals by the bio-PRB, depressing the focusing phenomenon. TG-2 depressed the focusing phenomenon the most because Cu2+ and Pb2+ can combine with not only CO32- but PO43-. The removal efficiency of Cu and Pb is 34% and 36%, respectively. A NH4+ recovery of about 100% is attained.

JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation.

Janus tyrosine kinase 3 (JAK3) is primarily expressed in immune cells and is needed for signaling by the common gamma chain (γc) family of cytokines. Abnormal JAK3 signal transduction can manifest as hematological disorders, e.g., leukemia, severe combined immunodeficiency (SCID) and autoimmune disease states. While regulatory JAK3 phosphosites have been well studied, here a functional proteomics approach coupling a JAK3 autokinase assay to mass spectrometry revealed ten previously unreported autophosphorylation sites (Y105, Y190, Y238, Y399, Y633, Y637, Y738, Y762, Y824, and Y841). Of interest, Y841 was determined to be evolutionarily conserved across multiple species and JAK family members, suggesting a broader role for this residue. Phospho-substitution mutants confirmed that Y841 is also required for STAT5 tyrosine phosphorylation. The homologous JAK1 residue Y894 elicited a similar response to mutagenesis, indicating the shared importance for this site in JAK family members. Phospho-specific Y841-JAK3 antibodies recognized activated kinase from various T-cell lines and transforming JAK3 mutants. Computational biophysics analysis linked Y841 phosphorylation to enhanced JAK3 JH1 domain stability across pH environments, as well as to facilitated complementary electrostatic JH1 dimer formation. Interestingly, Y841 is not limited to tyrosine kinases, suggesting it represents a conserved ubiquitous enzymatic function that may hold therapeutic potential across multiple kinase families.

DsbA-L deletion attenuates LPS-induced acute kidney injury by modulating macrophage polarization.

Disulfide bond A oxidoreductase-like protein (DsbA-L) drives acute kidney injury (AKI) by directly upregulating the expression of voltage-dependent anion-selective channels in proximal tubular cells. However, the role of DsbA-L in immune cells remains unclear. In this study, we used an LPS-induced AKI mouse model to assess the hypothesis that DsbA-L deletion attenuates LPS-induced AKI and explore the potential mechanism of DsbA-L action. After 24 hours of LPS exposure, the DsbA-L knockout group exhibited lower serum creatinine levels compared to the WT group. Furthermore, peripheral levels of the inflammatory cytokine IL-6 were decreased. Transcriptomic data analysis revealed a significant down-regulation in the IL-17 and tumor necrosis factor pathways in DsbA-L knockout mice following LPS induction. Metabolomic analysis suggested that arginine metabolism was significantly different between the WT and DsbA-L knockout groups after LPS treatment. Notably, the M1 polarization of macrophages in the kidneys of DsbA-L knockout AKI mice was significantly reduced. Expression of the transcription factors NF-κB and AP-1 was downregulated after DsbA-L knockout. Our results suggest that DsbA-L regulates LPS-mediated oxidative stress, promotes M1 polarization of macrophages, and induces expression of inflammatory factors via the NF-κB/AP-1 pathway.

Unraveling a blockchain-based framework towards patient empowerment: A scoping review envisioning future smart health technologies.

The COVID-19 pandemic shows us how crucial patient empowerment can be in the healthcare ecosystem. Now, we know that scientific advancement, technology integration, and patient empowerment need to be orchestrated to realize future smart health technologies. In that effort, this paper unravels the Good (advantages), Bad (challenges/limitations), and Ugly (lacking patient empowerment) of the blockchain technology integration in the Electronic Health Record (EHR) paradigm in the existing healthcare landscape. Our study addresses four methodically-tailored and patient-centric Research Questions, primarily examining 138 relevant scientific papers. This scoping review also explores how the pervasiveness of blockchain technology can help to empower patients in terms of access, awareness, and control. Finally, this scoping review leverages the insights gleaned from this study and contributes to the body of knowledge by proposing a patient-centric blockchain-based framework. This work will envision orchestrating three essential elements with harmony: scientific advancement (Healthcare and EHR), technology integration (Blockchain Technology), and patient empowerment (access, awareness, and control).

Phosphorylation of Tyrosine 841 Plays a Significant Role in JAK3 Activation.

Janus Kinase 3 (JAK3) plays a key role in the development, proliferation, and differentiation of various immune cells. It regulates gene expression by phosphorylation of Signal Transducers and Activators of Transcriptions (STATs) via the JAK/STAT pathway. Recently, we found a new JAK3 phosphorylation site, tyrosine 841 (Y841). The results showed that pY841 helps the kinase domain flip around the pseudo kinase domain, which may cause JAK3 conformational changes. It also reduces the size of the cleft between the N-lobe and the C-lobe of the JAK3 kinase domain. However, pY841 was found to enlarge the cleft when ATP/ADP was bound to the kinase. The increase in the cleft size suggested that pY841 enhanced the elasticity of the kinase domain. For unphosphorylated JAK3 (JAK3-Y841), the binding forces between the kinase domain and ATP or ADP were similar. After phosphorylation of Y841, JAK3-pY841 exhibited more salt bridges and hydrogen bonds between ATP and the kinase than between ADP and the kinase. Consequently, the electrostatic binding force between ATP and the kinase was higher than that between ADP and the kinase. The result was that compared to ADP, ATP was more attractive to JAK3 when Y841 was phosphorylated. Therefore, JAK3-pY841 tended to bind ATP rather than ADP. This work provides new insights into the role of phosphorylation in kinase activation and ATP hydrolysis and sheds light on the importance of understanding the molecular mechanisms that regulate the kinase function.

Immobilizing lead and copper in aqueous solution using microbial- and enzyme-induced carbonate precipitation.

Inappropriate irrigation could trigger migration of heavy metals into surrounding environments, causing their accumulation and a serious threat to human central nervous system. Traditional site remediation technologies are criticized because they are time-consuming and featured with high risk of secondary pollution. In the past few years, the microbial-induced carbonate precipitation (MICP) is considered as an alternative to traditional technologies due to its easy maneuverability. The enzyme-induced carbonate precipitate (EICP) has attracted attention because bacterial cultivation is not required prior to catalyzing urea hydrolysis. This study compared the performance of lead (Pb) and copper (Cu) remediation using MICP and EICP respectively. The effect of the degree of urea hydrolysis, mass and species of carbonate precipitation, and chemical and thermodynamic properties of carbonates on the remediation efficiency was investigated. Results indicated that ammonium ion (NH4 +) concentration reduced with the increase in lead ion (Pb2+) or copper ion (Cu2+) concentration, and for a given Pb2+ or Cu2+ concentration, it was much higher under MICP than EICP. Further, the remediation efficiency against Cu2+ is approximately zero, which is way below that against Pb2+ (approximately 100%). The Cu2+ toxicity denatured and even inactivated the urease, reducing the degree of urea hydrolysis and the remediation efficiency. Moreover, the reduction in the remediation efficiency against Pb2+ and Cu2+ appeared to be due to the precipitations of cotunnite and atacamite respectively. Their chemical and thermodynamic properties were not as good as calcite, cerussite, phosgenite, and malachite. The findings shed light on the underlying mechanism affecting the remediation efficiency against Pb2+ and Cu2+.

Early growth response-1: Key mediators of cell death and novel targets for cardiovascular disease therapy.

Significance: Cardiovascular diseases are seen to be a primary cause of death, and their prevalence has significantly increased across the globe in the past few years. Several studies have shown that cell death is closely linked to the pathogenesis of cardiovascular diseases. Furthermore, many molecular and cellular mechanisms are involved in the pathogenesis of the cardiac cell death mechanism. One of the factors that played a vital role in the pathogenesis of cardiac cell death mechanisms included the early growth response-1 (Egr-1) factor. Recent Advances: Studies have shown that abnormal Egr-1 expression is linked to different animal and human disorders like heart failure and myocardial infarction. The biosynthesis of Egr-1 regulates its activity. Egr-1 can be triggered by many factors such as serum, cytokines, hormones, growth factors, endotoxins, mechanical injury, hypoxia, and shear stress. It also displays a pro-apoptotic effect on cardiac cells, under varying stress conditions. EGR1 mediates a broad range of biological responses to oxidative stress and cell death by combining the acute changes occurring in the cellular environment with sustained changes in gene expression. Future Directions: The primary regulatory role played by the Egr-1-targeting DNAzymes, microRNAs, and oligonucleotide decoy strategies in cardiovascular diseases were identified to provide a reference to identify novel therapeutic targets for cardiovascular diseases.

Ligand-Directed Photocatalysts and Far-Red Light Enable Catalytic Bioorthogonal Uncaging inside Live Cells.

Described are ligand-directed catalysts for live-cell, photocatalytic activation of bioorthogonal chemistry. Catalytic groups are localized via a tethered ligand either to DNA or to tubulin, and red light (660 nm) photocatalysis is used to initiate a cascade of DHTz oxidation, intramolecular Diels-Alder reaction, and elimination to release phenolic compounds. Silarhodamine (SiR) dyes, more conventionally used as biological fluorophores, serve as photocatalysts that have high cytocompatibility and produce minimal singlet oxygen. Commercially available conjugates of Hoechst dye (SiR-H) and docetaxel (SiR-T) are used to localize SiR to the nucleus and microtubules, respectively. Computation was used to assist the design of a new class of redox-activated photocage to release either phenol or n-CA4, a microtubule-destabilizing agent. In model studies, uncaging is complete within 5 min using only 2 µM SiR and 40 µM photocage. In situ spectroscopic studies support a mechanism involving rapid intramolecular Diels-Alder reaction and a rate-determining elimination step. In cellular studies, this uncaging process is successful at low concentrations of both the photocage (25 nM) and the SiR-H dye (500 nM). Uncaging n-CA4 causes microtubule depolymerization and an accompanying reduction in cell area. Control studies demonstrate that SiR-H catalyzes uncaging inside the cell, and not in the extracellular environment. With SiR-T, the same dye serves as a photocatalyst and the fluorescent reporter for microtubule depolymerization, and with confocal microscopy, it was possible to visualize microtubule depolymerization in real time as the result of photocatalytic uncaging in live cells.

New nomogram for predicting lymph node positivity in pancreatic head cancer.

Background: Pancreatic cancer is one of the most malignant cancers worldwide, and it mostly occurs in the head of the pancreas. Existing laparoscopic pancreaticoduodenectomy (LPD) surgical techniques have has undergone a learning curve, a wide variety of approaches for the treatment of pancreatic cancer have been proposed, and the operation has matured. At present, pancreatic head cancer has been gradually changing from "surgeons' evaluation of anatomical resection" to "biologically inappropriate resection". In this study, the risk of lymph node metastasis in pancreatic head cancer was predicted using common preoperative clinical indicators. Methods: The preoperative clinical data of 191 patients with pancreatic head cancer who received LPD in the First Affiliated Hospital of Jilin University from May 2016 to December 2021 were obtained. A univariate regression analysis study was conducted, and the indicators with a significance level of P<0.05 were included in the univariate logistic regression analysis into multivariate. Lastly, a nomogram was built based on age, tumor size, leucocyte,albumin(ALB), and lymphocytes/monocytes(LMR). The model with the highest resolution was selected by obtaining the area under a curve. The clinical net benefit of the prediction model was examined using decision curve analyses.Risk stratification was performed by combining preoperative CT scan with existing models. Results: Multivariate logistic regression analysis found age, tumor size, WBC, ALB, and LMR as five independent factors. A nomogram model was constructed based on the above indicators. The model was calibrated by validating the calibration curve within 1000 bootstrap resamples. The ROC curve achieved an AUC of 0.745(confidence interval of 95%: 0.673-0.816), thus indicating that the model had excellent discriminative skills. DCA suggested that the predictive model achieved a high net benefit in the nearly entire threshold probability range. Conclusions: This study has been the first to investigate a nomogram for preoperative prediction of lymphatic metastasis in pancreatic head cancer. The result suggests that age, ALB, tumor size, WBC, and LMR are independent risk factors for lymph node metastasis in pancreatic head cancer. This study may provide a novel perspective for the selection of appropriate continuous treatment regimens, the increase of the survival rate of patients with pancreatic head cancer, and the selection of appropriate neoadjuvant therapy patients.

Investigating immobilization efficiency of Pb in solution and loess soil using bio-inspired carbonate precipitation.

Lead (Pb) metal accumulation in surrounding environments can cause serious threats to human health, causing liver and kidney function damage. This work explored the potential of applying the MICP technology to remediate Pb-rich water bodies and Pb-contaminated loess soil sites. In the test tube experiments, the Pb immobilization efficiency of above 85% is attained through PbCO3 and Pb(CO3)2(OH)2 precipitation. Notwithstanding that, in the loess soil column tests, the Pb immobilization efficiency decreases with the increase in depth and could be as low as approximately 40% in the deep ground. PbCO3 and Pb(CO3)2(OH)2 precipitation has not been detected as the majority of Pb2+ combines with -OH (hydroxyl group) when subjected to 500 mg/kg Pb2+. The alkaline front promotes the chemisorption of Pb2+ with CO32- reducing the depletion of quartz mineral close to the surface. However, OH- is in shortage in the deep ground retarding the Pb immobilization. The Pb immobilization efficiency thus decreases with the increase in depth. Quartz and albite minerals, when subjected to 16,000 mg/kg Pb2+, appear not to intervene in the chemisorption with Pb2+ where the chemisorption of Pb2+ with CO32- plays a major role in the Pb immobilization. Compared to the nanoscale urease applied to the enzyme-induced carbonate precipitation (EICP) technology, the micrometer scale ureolytic bacteria penetrate into the deep ground with difficulty. The 'size' issue remains to be addressed in near future.

HIT-2: Implementing machine learning algorithms to treat bound ions in biomolecules.

Electrostatic features are fundamental to protein functions and protein-protein interactions. Studying highly charged biomolecules is challenging given the heterogeneous distribution of the ionic cloud around such biomolecules. Here we report a new computational method, Hybridizing Ions Treatment-2 (HIT-2), which is used to model biomolecule-bound ions using the implicit solvation model. By modeling ions, HIT-2 allows the user to calculate important electrostatic features of the biomolecules. HIT-2 applies an efficient algorithm to calculate the position of bound ions from molecular dynamics simulations. Modeling parameters were optimized by machine learning methods from thousands of datasets. The optimized parameters produced results with errors lower than 0.2 Å. The testing results on bound Ca2+ and Zn2+ in NAMD simulations also proved that HIT-2 can effectively identify bound ion types, numbers, and positions. Also, multiple tests performed on HIT-2 suggest the method can handle biomolecules that undergo remarkable conformational changes. HIT-2 can significantly improve electrostatic calculations for many problems in computational biophysics.