The prevalence and genotypes of Cryptosporidium spp. in bar-headed goose (Anser indicus) in China.

Cryptosporidium spp. is an important foodborne and waterborne pathogen in humans and animals, causing diarrhoea in humans and respiratory and gastrointestinal diseases in birds. However, reports of Cryptosporidium infection in bar-headed goose are limited. To determine the infection rate and species/genotypes of Cryptosporidium in bar-headed goose in China, a total of 358 fecal samples were collected from 3 regions. Nested PCR was used to amplify Cryptosporidium SSU rRNA regions from the fecal extracted-DNA samples. The total infection rate of Cryptosporidium in bar-headed in China was 3.9 % (14/358), with 4.2 % (5/120) in Aba (Ngawa) Tibetan and Qiang Autonomous Prefect, Sichuan province, 7.6 % (9/119) in Maqu county, Gansu province, and 0.0 % (0/119) in Caohai, Wei ning county, Guizhou province. The differences in prevalence rate by region were statistically significant. All positive samples were identified as Cryptosporidium goose genotype I (n = 14). This is the first systematic investigation of the epidemiological status and dominant species/genotypes of Cryptosporidium in bar-headed goose in China, thereby enhancing our understanding of the epidemiology of Cryptosporidium infection in wild migratory birds.

Association of Serum Unsaturated Fatty Acid Patterns with the Risk of Diabetic Nephropathy.

Introduction: Unsaturated fatty acids play an essential role in the progression of diabetic nephropathy (DN). However, previous studies were mainly focused on the role of individual unsaturated fatty acid. The serum unsaturated fatty acid patterns (FAPs) in patients with DN remain to be determined. Methods: A total of 135 patients with DN (DN group) and 322 patients with type II diabetes without nephropathy (non-DN group) were included in this study. Clinical data, serum levels of unsaturated fatty acids, and other laboratory indicators were collected. Multivariate logistic regression was applied to identify risk factors for serum unsaturated fatty acid level in both groups. Serum unsaturated fatty acids were subjected to factor analysis to identify distinct FAPs. Multivariable logistic regression was employed to assess the risk of DN associated with different serum FAPs. Results: After adjusting for confounders, three types of unsaturated fatty acid including C20:5 (eicosapentaenoic acid [EPA]), C22:6 (docosahexaenoic acid [DHA]), and C22:5 n-3 (docosapentaenoic acid n-3) were significantly associated with DN in the population. The odds ratios (ORs) (95% confidence interval [CI]) of DN were 0.583 (0.374, 0.908), 0.826 (0.716, 0.954), and 0.513 (0.298, 0.883), respectively. Factor analysis revealed five major FAPs, among which FAP2 (enriched with EPA and DHA) exhibited a significant inverse association with DN. In the multivariate-adjusted model, the OR (95% CI) was 0.678 (0.493, 0.933). Additionally, a combination of DHA and EPA enriched in FAP2 further decreased extracellular matrix production induced by transforming growth factor beta 1 in podocytes and tubular cells. Conclusions: Our findings suggest that FAP2 which is enriched with DHA and EPA is associated with a reduced risk of DN. This highlights the potential of targeting FAP2 for the patients with DN.

CRISPR/Cas9-Mediated Knockout of the PxJHBP Gene Resulted in Increased Susceptibility to Bt Cry1Ac Protoxin and Reduced Lifespan and Spawning Rates in Plutella xylostella.

Juvenile hormone binding protein (JHBP) is a key regulator of JH signaling, and crosstalk between JH and 20-hydroxyecdysone (20E) can activate and fine-tune the mitogen-activated protein kinase cascade, leading to resistance to insecticidal proteins from Bacillis thuringiensis (Bt). However, the involvement of JHBP in the Bt Cry1Ac resistance of Plutella xylostella remains unclear. Here, we cloned a full-length cDNA encoding JHBP, and quantitative real-time PCR (qPCR) analysis showed that the expression of the PxJHBP gene in the midgut of the Cry1Ac-susceptible strain was significantly higher than that of the Cry1Ac-resistant strain. Furthermore, CRISPR/Cas9-mediated knockout of the PxJHBP gene significantly increased Cry1Ac susceptibility, resulting in a significantly shorter lifespan and reduced fertility. These results demonstrate that PxJHBP plays a critical role in the resistance to Cry1Ac protoxin and in the regulation of physiological metabolic processes associated with reproduction in adult females, providing valuable insights to improve management strategies of P. xylostella.

Development and validation of a nomogram to predict intracranial haemorrhage in neonates.

BACKGROUND: The aim of this study was to establish and validate a Susceptibility-weighted imaging (SWI)-based predictive model for neonatal intracranial haemorrhage (ICH). METHODS: A total of 1190 neonates suspected of ICH after cranial ultrasound screening in a tertiary hospital were retrospectively enrolled. The neonates were randomly divided into a training cohort and a internal validation cohort by a ratio of 7:3. Univariate analysis was used to analyze the correlation between risk factors and ICH, and the prediction model of neonatal ICH was established by multivariate logistic regression based on minimum Akaike information criterion (AIC). The nomogram was externally validated in another tertiary hospital of 91 neonates. The performance of the nomogram was evaluated in terms of discrimination by the area under the curve (AUC), calibration by the calibration curve and clinical net benefit by the decision curve analysis (DCA). RESULTS: Univariate analysis and min AIC-based multivariate logistic regression screened the following variables to establish a predictive model for neonatal ICH: Platelet count (PLT), gestational diabetes, mode of delivery, amniotic fluid contamination, 1-min Apgar score. The AUC was 0.715, 0.711, and 0.700 for the training cohort, internal validation cohort, and external validation cohort, respectively. The calibration curve showed a good correlation between the nomogram prediction and actual observation for ICH. DCA showed the nomogram was clinically useful. CONCLUSION: We developed and validated an easy-to-use nomogram to predict ICH for neonates. This model could support individualized risk assessment and healthcare.

Phaeohyphomycosis caused by Corynespora cassiicola, a plant pathogen worldwide.

Although rare, trans-kingdom infection features an interesting infection biology concept, in which highly versatile pathogenic attributes allow successful infections in evolutionarily highly divergent species. Corynespora cassiicola is a phytopathogenic fungus and occasionally causes human infections. Herein, we report a phaeohyphomycosis case caused by C. cassiicola. Given that sporadic reports may contribute to a lack of awareness of the transmission route, clinical manifestations, and diagnostic and clinical management, we systematically reviewed the cases reported thus far. Nine patients were identified and included in the pooled analysis, 88.9% (8/9) of whom were reported after 2010. All patients were from Asian, African, and Latin American countries, among whom 77.8% (7/9) were farmers or lived in areas with active agriculture. Exposed body parts were the major affected infection area, and clinical manifestations were mainly non-specific inflammatory reactions. Although biochemical and morphological examinations confirmed the presence of fungal infection, molecular analysis was used for the final diagnosis, with 77.8% (7/9) being identified by internal transcribed spacer sequencing. Whereas voriconazole, terbinafine, and AmB, either alone or in combination, resulted in successful infection resolution in most cases (5/9; 55.5%), those suffering from invasive facial infections and CARD9 deficiency showed poor outcomes. Our patient is the third case of invasive facial infection caused by C. cassiicola and was successfully treated with intravenous LAmB followed by oral voriconazole combined with topical antifungal irrigation. Molecular identification of fungus and prompt antifungal treatment is pivotal in the clinical success of patients suspected to have phaeohyphomycosis. Moreover, as evidenced by our data, itraconazole treatment is not recommended.

Inhibition of HDAC6 with CAY10603 alleviates acute and chronic kidney injury by suppressing the ATF6 branch of UPR.

BACKGROUND: Histone deacetylase 6 (HDAC6) inhibitor CAY10603 has been identified as a potential therapeutic agent for the treatment of diabetic kidney disease (DKD). The objective of this study was to investigate the therapeutic effects of CAY10603 in mice with acute kidney injury (AKI) and chronic kidney diseases (CKD). METHODS: Renal immunohistology was performed to assess the expression levels of HDAC6 in both human and mouse kidney samples. C57BL/6J mice were intraperitoneal injected with lipopolysaccharide (LPS) to induce AKI; CD-1 mice were fed with adenine diet to induce adenine-nephropathy as CKD model. Serum creatinine, blood urea nitrogen and uric acid were measured to reflect renal function; renal histology was applied to assess kidney damage. Western blot and immunohistology were used to analyze the unfolded protein response (UPR) level. RESULTS: HDAC6 was significantly upregulated in renal tubular epithelial cells (RTECs) of both AKI and CKD patients as well as mice. In the murine models of AKI induced by LPS and adenine-induced nephropathy, CAY10603 exhibited notable protective effects, including improvement in biochemical indices and pathological changes. In vivo and in vitro studies revealed that CAY10603 effectively suppressed the activation of activating transcription factor 6 (ATF6) branch of UPR triggered by thapsigargin (Tg), a commonly employed endoplasmic reticulum (ER) stressor. Consistent with these findings, CAY10603 also displayed substantial inhibition of ATF6 activation in RTECs from both murine models of LPS-induced AKI and adenine-induced nephropathy. CONCLUSIONS: Collectively, these results suggest that CAY10603 holds promise as a potential therapeutic agent for both acute and chronic kidney injury.

A Hybrid-Salt Strategy for Modulating the Li+ Solvation Sheathes and Constructing Robust SEI in Non-Flammable Electrolyte Lithium Metal Batteries.

The electrode interface determines the performance of an electrochemical energy storage system. Using traditional electrolyte organic additives and high-concentration electrolyte emerging recently are two generally strategies for improving the electrode interface. Here, a hybrid-salt electrolyte strategy is proposed for constructing the stable electrode interface. Through the solubilization effect of phosphate ester on LiNO3, a hybrid-salts-based non-flammable phosphate ester electrolyte system (HSPE) with LiPF6 and LiNO3 as Li salts has been developed. By the strong interaction between NO3 - and Li+, the Li+ solvation sheath and solvent behaviors have been modulated, thus the undesirable effects of phosphate ester are eliminated and a robust SEI is formed. Experimental results and theoretical calculations illustrate that NO3 - as a kind of strongly coordinating anion can reduce the number of TEP molecules and lower the reduction reactivity of TEP. The reconfigured Li+ solvation structure allows the formation of an inorganic-rich SEI on the electrode surface. As a result, in the designed HSPE, the average coulombic efficiency of lithium plating/stripping is increased to 99.12 %. This work explored a new approach to construct the electrode interface and addressing the poor interface performance issue of phosphate esters.

Allulose mitigates chronic enteritis by reducing mitochondria dysfunction via regulating cathepsin B production.

Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10-/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.

Impact of the peripheral blood inflammatory indices and modified nomogram-revised risk index on survival of Extranodal Nasal-Type Natural Killer/T-Cell lymphoma.

BACKGROUND: At present, peripheral blood markers are easily accessible information and clinically valuable prognostic indicators in extranodal nasal-type natural killer/T-cell lymphoma (ENKTCL). Nevertheless, the role of its comprehensive score in ENKTCL remains to be determined. OBJECTIVE: Therefore, this study aimed to investigate the prognostic effect of the peripheral inflammation score on ENKTCL. METHODS: The retrospective study included 183 patients with ENKTCL. Univariate Cox regression analyses and least absolute shrinkage and selection operator (LASSO) Cox regression were used to construct the inflammation-related prognostic index named Risk. Univariate and multivariate Cox regression analyses and regression adjustment with propensity score matching (PSM) were used to evaluate the prognostic ability of risk. The performance of the modified nomogram-revised risk index (NRI) by integrating risk was evaluated with the area under the time-dependent receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and integrated Brier score (IBS). RESULTS: The risk cut-off value, constructed by the lymphocyte count, platelet count, albumin level, LMR, and PNI, was -1.3486. Before PSM, multivariate analysis showed that risk was significantly associated with OS (HR = 2.577, 95% CI = 1.614-4.114, P< 0.001) and PFS (HR = 2.679, 95% CI = 1.744-4.114, P< 0.001). After PSM adjustment, risk was still an independent factor for OS (HR = 2.829, 95% CI = 1.601-5.001, P< 0.001) and PFS (HR = 2.877, 95% CI = 1.735-4.770, P< 0.001). With the NRI, the modified NRI by integrating risk increased the AUC and clinical net benefit and decreased the IBS. CONCLUSIONS: Risk is an easily accessible and inexpensive indicator that may be used as a prognostic marker and could improve NRI predictive power in patients with ENKTCL.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Serum aspartate aminotransferase, a novel potential biomarker of prognosis in extranodal natural killer/T cell lymphoma, nasal type.

BACKGROUND: Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. OBJECTIVE: This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). METHODS: We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups' overall survival (OS) and progression-free survival (PFS). RESULTS: Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. CONCLUSION: AST might represent a significant prognostic marker for ENKTL patients.

Palmitoyltransferase DHHC9 and acyl protein thioesterase APT1 modulate renal fibrosis through regulating ß-catenin palmitoylation.

palmitoylation, a reversible post-translational modification, is initiated by the DHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases. However, the role and mechanisms for protein palmitoylation in renal fibrosis have not been elucidated. Here we show protein palmitoylation and DHHC9 were downregulated in the fibrotic kidneys of mouse models and chronic kidney disease (CKD) patients. Ablating DHHC9 in tubular cells aggravated, while inducing DHHC9 overexpression with adeno-DHHC9 transfection or iproniazid treatment protected against kidney fibrosis in male mouse models. Mechanistically, DHHC9 palmitoylated ß-catenin, thereby promoted its ubiquitination and degradation. Additionally, acyl protein thioesterase 1 (APT1) was induced in the fibrotic kidneys, which depalmitoylated ß-catenin, increased its abundance and nuclear translocation. Ablating tubular APT1 or inhibiting APT1 with ML348 markedly protected against unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI)-induced kidney fibrosis in male mice. This study reveals the regulatory mechanism of protein palmitoylation in kidney fibrosis.

Enhancing sludge methanogenesis with changed micro-environment of anaerobic microorganisms by Fenton iron mud.

Conductive materials have been demonstrated to enhance sludge methanogenesis, but few researches have concentrated on the interaction among conductive materials, microorganisms and their immediate living environment. In this study, Fenton iron mud with a high abundance of Fe(III) was recycled and applied in anaerobic reactors to promote anaerobic digestion (AD) process. The results show that the primary content of extracellular polymeric substances (EPS) such as polysaccharides and proteins increased significantly, possibly promoting microbial aggregation. Furthermore, with the increment of redox mediators including humic substances in EPS and Fe(III) introduced by Fenton iron mud, the direct interspecies electron transfer (DIET) between methanogens and interacting bacteria could be accelerated, which enhanced the rate of methanogenesis in anaerobic digestion (35.21 ± 4.53% increase compared to the control). The further analysis of the anaerobic microbial community confirmed the fact that Fenton iron mud enriched functional microorganisms, such as the abundance of CO2-reducing (e.g. Chloroflexi) and Fe(III)-reducing bacteria (e.g., Tepidimicrobium), thereby expediting the electron transfer reaction in the AD process via microbial DIET and dissimilatory iron reduction (DIR). This work will make it possible for using the recycled hazardous material - Fenton iron mud to improve the performance of anaerobic granular sludge during methanogenesis.

Application of Familial Y-STR Haplotype Mismatch Tolerance in Genealogy Inference.

OBJECTIVES: To provide a guideline for genealogy inference and family lineage investigation through a study of the mismatch tolerance distribution of Y-STR loci in Chinese Han male lineage. METHODS: Three Han lineages with clear genetic relationships were selected. YFiler Platinum PCR amplification Kit was used to obtain the typing data of 35 Y-STR loci in male samples. The variation of Y-STR haplotypes in generation inheritance and the mismatch tolerance at 1-7 kinship levels were statistically analyzed. RESULTS: Mutations in Y-STR were family-specific with different mutation loci and numbers of mutation in different lineages. Among all the mutations, 66.03% were observed on rapidly and fast mutating loci. At 1-7 kinship levels, the number of mismatch tolerance ranged from 0 to 5 on all 35 Y-STR loci, with a maximum step size of 6. On medium and slow mutant loci, the number of mismatch tolerance ranged from 0 to 2, with a maximum step size of 3; on rapidly and fast mutant loci, the number of mismatch tolerance ranged from 0 to 3, with a maximum step size of 6. CONCLUSIONS: Combined use of SNP genealogy inference and Y-STR lineage investigation, both 0 and multiple mismatch tolerance need to be considered. Family lineage with 0-3 mismatch tolerance on all 35 Y-STR loci and 0-1 mismatch tolerance on medium and slow loci can be prioritized for screening. When the number of mismatch tolerance is eligible, family lineages with long steps should be carefully excluded. Meanwhile, adding fast mutant loci should also be handled with caution.

An Endogenous Prompting Mechanism for Sulfur Conversions Via Coupling with Polysulfides in Li-S Batteries.

The sluggish kinetics process and shuttling of soluble intermediates present in complex conversion between sulfur and lithium sulfide severely limit the practical application of lithium-sulfur batteries. Herein, by introducing a designated functional organic molecule to couple with polysulfide intermediators, an endogenous prompting mechanism of sulfur conversions has thus been created leading to an alternative sulfur-electrode process, in another words, to build a fast "internal cycle" of promotors that can promote the slow "external cycle" of sulfur conversions. The coupling-intermediators between the functional organic molecule and polysulfides, organophosphorus polysulfides, to be the "promotors" for sulfur conversions, are not only insoluble in the electrolyte but also with higher redox-activity. So the sulfur-electrode process kinetics is greatly improved and the shuttle effect is eliminated simultaneously by this strategy. Meanwhile, with the endogenous prompting mechanism, the morphology of the final discharge product can be modified into a uniform covering film, which is more conducive to its decomposition when charging. Benefiting from the effective mediation of reaction kinetics and control of intermediates solubility, the lithium-sulfur batteries can act out excellent rate performance and cycling stability.

Ultrafast and Ultralarge Lithium-Ion Storage Enabled by Fluorine-Nitrogen Co-Implanted Carbon Tubes.

As a holy grail in electrochemistry, both high-power and high-energy electrochemical energy storage system (EES) has always been a pursued dream. To simultaneously achieve the "both-high" EES, a rational design of structure and composition for storage materials with characteristics of battery-type and capacitor-type storage is crucial. Herein, fluorine-nitrogen co-implanted carbon tubes (FNCT) have been designed, in which plentiful active sites and expanded interlayer space have been created benefiting from the heteroatom engineering and the fluorine-nitrogen synergistic effect, thus the above two-type storage mechanism can get an optimal balance in the FNCT. The implanted fluorine heteroatoms can not only amplify interlayer spacing, but also induce the transformation of nitrogen configuration from pyrrole nitrogen to pyridine nitrogen, further promoting the activity of the carbon matrix. The extraordinary electrochemical performance as results can be witnessed for FNCT, which exhibit fast lithium-ion storage capability with a high energy density of 119.4 Wh kg-1 at an ultrahigh power density of 107.5 kW kg-1 .

Clip-SP1 cleavage activates downstream prophenoloxidase activating protease (PAP) in Plutella xylostella.

Melanization is a component of the humoral immune defense of insects and is induced by serine protease-mediated phenoloxidase (PO) catalysis. Prophenoloxidase (PPO) in the midgut of Plutella xylostella is activated by the CLIP domain serine protease (clip-SP) in response to Bacillus thuringiensis (Bt) infection, but the detailed signaling cascade following this activation is unknown. Here, we report that activation of clip-SP enhances PO activity in the P. xylostella midgut by cleaving three downstream PPO-activating proteases (PAPs). First, the expression level of clip-SP1 was increased in the midgut after Bt8010 infection of P. xylostella. Then, purified recombinant clip-SP1 was able to activate three PAPs - PAPa, PAPb and PAP3 - which in turn enhanced their PO activity in the hemolymph. Furthermore, clip-SP1 showed a dominant effect on PO activity compared to the individual PAPs. Our results indicate that Bt infection induces the expression of clip-SP1, which is upstream of a signaling cascade, to efficiently activate PO catalysis and mediate melanization in the midgut of P. xylostella. And it provides a basis for studying the complex PPO regulatory system in the midgut during Bt infection.

Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems.

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms.  This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'.

Analysis of the Effect of Plutella xylostella Polycalin and ABCC2 Transporter on Cry1Ac Susceptibility by CRISPR/Cas9-Mediated Knockout.

Many insects, including the Plutella xylostella (L.), have developed varying degrees of resistance to many insecticides, including Bacillus thuringiensis (Bt) toxins, the bioinsecticides derived from Bt. The polycalin protein is one of the potential receptors for Bt toxins, and previous studies have confirmed that the Cry1Ac toxin can bind to the polycalin protein of P. xylostella, but whether polycalin is associated with the resistance of Bt toxins remains controversial. In this study, we compared the midgut of larvae from Cry1Ac-susceptible and -resistant strains, and found that the expression of the Pxpolycalin gene was largely reduced in the midgut of the resistant strains. Moreover, the spatial and temporal expression patterns of Pxpolycalin showed that it was mainly expressed in the larval stage and midgut tissue. However, genetic linkage experiments showed that the Pxpolycalin gene and its transcript level were not linked to Cry1Ac resistance, whereas both the PxABCC2 gene and its transcript levels were linked to Cry1Ac resistance. The larvae fed on a diet containing the Cry1Ac toxin showed no significant change in the expression of the Pxpolycalin gene in a short term. Furthermore, the knockout of polycalin and ATP-binding cassette transporter subfamily C2 (ABCC2) genes separately by CRISPR/Cas9 technology resulted in resistance to decreased susceptibility to Cry1Ac toxin. Our results provide new insights into the potential role of polycalin and ABCC2 proteins in Cry1Ac resistance and the mechanism underlying the resistance of insects to Bt toxins.

Multiscale QM/MM modelling of catalytic systems with ChemShell.

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling.