Gut microbiota carcinogen metabolism causes distal tissue tumours.

Exposure to environmental pollutants and human microbiome composition are important predisposition factors for tumour development1,2. Similar to drug molecules, pollutants are typically metabolized in the body, which can change their carcinogenic potential and affect tissue distribution through altered toxicokinetics3. Although recent studies demonstrated that human-associated microorganisms can chemically convert a wide range of xenobiotics and influence the profile and tissue exposure of resulting metabolites4,5, the effect of microbial biotransformation on chemical-induced tumour development remains unclear. Here we show that the depletion of the gut microbiota affects the toxicokinetics of nitrosamines, which markedly reduces the development and severity of nitrosamine-induced urinary bladder cancer in mice6,7. We causally linked this carcinogen biotransformation to specific gut bacterial isolates in vitro and in vivo using individualized bacterial culture collections and gnotobiotic mouse models, respectively. We tested gut communities from different human donors to demonstrate that microbial carcinogen metabolism varies between individuals and we showed that this metabolic activity applies to structurally related nitrosamine carcinogens. Altogether, these results indicate that gut microbiota carcinogen metabolism may be a contributing factor for chemical-induced carcinogenesis, which could open avenues to target the microbiome for improved predisposition risk assessment and prevention of cancer.

Unravelling the collateral damage of antibiotics on gut bacteria.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for ß-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3-5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.

Inhibiting Ion Migration and Stabilizing Crystal-Phase in Halide Perovskite via Directly Incorporated Fluoride Anion.

Fluoride anion (F-) with extremely high electronegativity has been under intensive investigation in perovskite solar cells due to its remarkable defect suppression and greatly improvement of device performance. Nevertheless, these researches only focus on surface, grain boundaries or interface modification, the directly insertion of F- into crystal lattice of regular lead halide perovskite films is still unrevealed. Herein, F- was successfully incorporated into perovskite lattice by overcoming the insolubility of PbF2 via the introduced pyridinium halide as a novel volatile solubilizing ligand. The strong electronegativity of F- can strongly increase the binding energy of all the ions in CsPbI2Br and inhibit their defect formations. A trace amount of F- incorporation not only enhanced the optoelectronic properties but also effectively mitigated the ion migration and phase separation simultaneously. The photovoltaic performance and operational stability of perovskite solar cells were significantly improved with a champion efficiency of 17.78% (38.01%) under AM 1.5G (1000 lux indoor light). Moreover, F- can also be directly inserted into hybrid perovskite lattice and greatly stabilized crystal-phase, enabling efficient fully MA-free FAPbI3 devices with 25.10% efficiency. Our strategy sheds light on F-containing perovskites and provides a promising way to tackle ion migration and stabilize crystal-phase in halide perovskites.

Prostaglandin E2 stimulates cAMP signaling and resensitizes human leukemia cells to glucocorticoid-induced cell death.

Glucocorticoid (GC) resistance remains a clinical challenge in pediatric acute lymphoblastic leukemia where response to GC is a reliable prognostic indicator. To identify GC resistance pathways, we conducted a genome-wide, survival-based, short hairpin RNA screen in murine T-cell acute lymphoblastic leukemia (T-ALL) cells. Genes identified in the screen interfere with cyclic adenosine monophosphate (cAMP) signaling and are underexpressed in GC-resistant or relapsed ALL patients. Silencing of the cAMP-activating Gnas gene interfered with GC-induced gene expression, resulting in dexamethasone resistance in vitro and in vivo. We demonstrate that cAMP signaling synergizes with dexamethasone to enhance cell death in GC-resistant human T-ALL cells. We find the E prostanoid receptor 4 expressed in T-ALL samples and demonstrate that prostaglandin E2 (PGE2) increases intracellular cAMP, potentiates GC-induced gene expression, and sensitizes human T-ALL samples to dexamethasone in vitro and in vivo. These findings identify PGE2 as a target for GC resensitization in relapsed pediatric T-ALL.

Decreased expression of RPL15 and RPL18 exacerbated the calcification of valve interstitial cells during aortic valve calcification.

Calcific aortic valve disease (CAVD) is the most common valvular heart disease, with an increasing prevalence due to an aging population. The pathobiology of CAVD is a multifaceted and actively regulated process, but the detailed mechanisms have not been elucidated. The present study aims to identify the differentially expressed genes (DEGs) in calcified aortic valve tissues, and to analyze the correlation between DEGs and clinical features in CAVD patients. The DEGs were screened by microarray in normal and CAVD groups (n = 2 for each group), and confirmed by quantitative real-time polymerase chain reaction in normal (n = 12) and calcified aortic valve tissues (n = 34). A total of 1048 DEGs were identified in calcified aortic valve tissues, including 227 upregulated mRNAs and 821 downregulated mRNAs. Based on multiple bioinformatic analyses, three 60S ribosomal subunit components (RPL15, RPL18, and RPL18A), and two 40S ribosomal subunit components (RPS15 and RPS21) were identified as the top 5 hub genes in the protein-protein interaction network of DEGs. The expression of RPL15 and RPL18 was also found significantly decreased in calcified aortic valve tissues (both p < .01), and negatively correlated with the osteogenic differentiation marker OPN in CAVD patients (both p < .01). Moreover, inhibition of RPL15 or RPL18 exacerbated the calcification of valve interstitial cells under osteogenic induction conditions. The present study proved that decreased expression of RPL15 and RPL18 was closely associated with aortic valve calcification, which provided valuable clues to find therapeutic targets for CAVD.

Mitral valve repair and concomitant maze procedure versus catheter ablation in the treatment of atrial functional mitral regurgitation.

BACKGROUND: To compare mitral valve (MV) repair and concomitant maze procedure with catheter ablation in treating patients with atrial functional mitral regurgitation (AFMR). METHODS: We retrospectively identified 126 patients with AFMR from January 2012 to December 2015. Of these patients, 60 patients underwent MV repair and concomitant maze procedure, and 66 patients received catheter ablation. Patients were followed up for 7.98 ± 2.01 years. The survival, readmission of heart failure (HF), persistent atrial fibrillation (AF), persistent moderate-severe mitral regurgitation (MR) and tricuspid Regurgitation (TR), and echocardiographic data were analyzed in the follow-up. Predictors of readmission of HF were analyzed. RESULTS: There was no significant difference in baseline and echocardiographic characteristics, in-hospital mortality, and other adverse events postoperatively between two groups. The surgical group was associated with lower rates of MR > 2 + grade either at discharge (P = 0.0023) or in the follow-up (P = 0.0001). There was no significant difference in the incidence of overall survival between the two groups. The surgical group was associated with a lower rate of readmission of HF and AF in the follow-up. Univariable and multivariable analysis confirmed AF at discharge, moderate-severe MR at discharge, no MV surgery, moderate-severe TR at discharge, and LA volume as predictors of readmission of HF. Both groups experienced significant reverse cardiac remodeling. CONCLUSIONS: Our results suggest that for the treatment of AFMR with persistent or long-standing persistent AF and moderate-severe MR, MV repair and concomitant maze procedure may achieve a better outcome than catheter ablation procedure.

Genetic variability and population diversity of the human SLCO (OATP) transporter family.

Organic anion transporting polypeptides (OATP) encoded by the SLCO gene family constitute clinically important transporters involved in the disposition of endogenous compounds and many commonly prescribed drugs, including statins, methotrexate and antihypertensive medications. Common genetic polymorphisms in SLCO genes are known to affect OATP function and modulate efficacy and safety of OATP substrates. However, current frequency data of these variants and haplotypes is generally based on few rather heterogenous populations of relatively small sample size. Furthermore, the genetic variability beyond these selected pharmacogenetic biomarkers has not been systematically analyzed. Here, we provide a global consolidated map of SLCO variability by leveraging fully compatible Next Generation Sequencing data from 138,632 unrelated individuals across seven major human populations. Overall, we find 9811 exonic single nucleotide variants and 155 copy number variations of which 99.3% were rare with frequencies <1%. Using orthogonal computational functionality predictors optimized for pharmacogenetic assessments, we find that four out of five individuals carry at least one deleterious variant in an SLCO transporter gene and rare variants contribute 23% to the genetically encoded functional variability. Moreover, 74.9% of all variants were found to be population-specific with important consequences for population-specific genotyping strategies and precision public health approaches. Combined, our analyses provide the most comprehensive data set of SLCO variability published to date and incentivize the integration of comprehensive NGS-based genotyping into personalized predictions of OATP substrate disposition.

RNA interference knockdown of aminopeptidase N genes decrease the susceptibility of Chilo suppressalis larvae to Cry1Ab/Cry1Ac and Cry1Ca-expressing transgenic rice.

Transgenic rice expressing Bacillus thuringiensis (Bt) Cry toxins are resistant to lepidopteran pests, such as Chilo suppressalis, a major insect pest of rice in Asia. Understanding how these toxins interact with their hosts is crucial to understanding their insecticidal action. In this study, knockdown of two aminopeptidase N genes (APN1 and APN2) by RNA interference resulted in decreased susceptibility of C. suppressalis larvae to the Bt rice varieties TT51 (Cry1Ab and Cry1Ac fusion genes) and T1C-19 (Cry1Ca), but not T2A-1 (Cry2Aa). This suggests that APN1 and APN2 are receptors for Cry1A and Cry1C toxins in C. suppressalis.

Cadherin is involved in the action of Bacillus thuringiensis toxins Cry1Ac and Cry2Aa in the beet armyworm, Spodoptera exigua.

Bacillus thuringiensis (Bt) insecticidal crystal (Cry) proteins are effective against some insect pests in sprays and transgenic crops, although the evolution of resistance could threaten the long-term efficacy of such Bt use. One strategy to delay resistance to Bt crops is to "pyramid" two or more Bt proteins that bind to distinct receptor proteins within the insect midgut. The most common Bt pyramid in cotton (Gossypium hirsutum L.) employs Cry1Ac with Cry2Ab to target several key lepidopteran pests, including the beet armyworm, Spodoptera exigua (Hübner), which is a serious migratory pest of many vegetable crops and is increasingly important in cotton in China. While cadherin and aminopeptidase-N are key receptors of Cry1 toxins in many lepidopterans including S. exigua, the receptor for Cry2A toxins remains poorly characterized. Here, we show that a heterologous expressed peptide corresponding to cadherin repeat 7 to the membrane proximal extracellular domain (CR7-MPED) in the S. exigua cadherin 1b (SeCad1b) binds Cry1Ac and Cry2Aa. Moreover, SeCad1b transcription was suppressed in S. exigua larvae by oral RNA interference and susceptibility to Cry1Ac and Cry2Aa was significantly reduced. These results indicate that SeCad1b plays important functional roles of both Cry1Ac and Cry2Aa, having major implications for resistance management for S. exigua in Bt crops.

Clinical application of early postoperative nutritional support in patients with high-risk valvular heart disease.

BACKGROUND: The treatment strategy of early nutritional support after cardiac surgery has gradually been adopted. However, there are no scientific guidelines for the timing and specific programs of early nutritional support. METHODS: A retrospective, single-center analysis (2021-2023) was carried out including elderly patients who were admitted for valvular heart disease (VHD) and received open-heart valve replacement surgery. We designated patients who started the optimized nutritional support after surgery as the EN group and those who received traditional nutritional support as the TN group. The nutritional and immune indexes, postoperative complications, length of hospital stay, and hospitalization cost of the two groups were compared and analyzed. RESULTS: We identified 378 eligible patients, comprising 193 (51%) patients in the EN group and 185 (49%) patients in the TN group. There was no significant difference in hospital mortality between the two groups, but the proportion of nosocomial pneumonia was significantly lower in the EN group than in the TN group (P < 0.001). In the Poisson regression analysis, EN was not associated with an increase in gastrointestinal complications (P = 0.549). The EN group also seemed to have shorter hospital stays and lower hospitalization expenses (P < 0.001). In the comparison of postoperative gastrointestinal complications, fewer patients experienced diarrhea (P = 0.021) and abdominal distension (P = 0.033) in the EN group compared with the TN group. CONCLUSION: The optimal nutritional support strategy could effectively improve the clinical outcome of high-risk patients with valvular heart disease.

Enhanced expression of miR-20a driven by nanog exacerbated the degradation of extracellular matrix in thoracic aortic dissection.

Thoracic aortic dissection (TAD) is a life-threatening vascular disease manifested as intramural bleeding in the medial layers of the thoracic aorta. The key histopathologic feature of TAD is medial degeneration, characterized by depletion of vascular smooth muscle cells (VSMCs) and degradation of extracellular matrix (ECM). MicroRNA, as essential epigenetic regulators, can inhibit the protein expression of target genes without modifying the sequences. This study aimed to elucidate the role and underlying mechanism of miR-20a, a member of the miR-17-92 cluster, in regulating ECM degradation during the pathogenesis of TAD. The expression of the miR-17-92 cluster was significantly increased in synthetic VSMCs derived from TAD lesions compared to contractile VSMCs isolated from normal thoracic aortas. Notably, the expression of miR-20a was increased in VSMCs in response to serum exposure and various stimuli. In TAD lesions, the expression of miR-20a was significantly negatively correlated with that of elastin. Elevated expression of miR-20a was also observed in thoracic aortas of TAD mice induced by ß-aminopropionitrile fumarate and angiotensin II. Overexpression of miR-20a via mimic transfection enhanced the growth and invasive capabilities of VSMCs, with no significant impact on their migratory activity or the expression of phenotypic markers (α-SMA, SM22, and OPN). Silencing of miR-20a with inhibitor transfection mitigated the hyperactivation of MMP2 in VSMCs stimulated by PDGF-bb, as evidenced by reduced levels of active-MMP2 and increased levels of pro-MMP2. Subsequently, TIMP2 was identified as a novel target gene of miR-20a. The role of miR-20a in promoting the activation of MMP2 was mediated by the suppression of TIMP2 expression in VSMCs. In addition, the elevated expression of miR-20a was found to be directly driven by Nanog in VSMCs. Collectively, these findings indicate that miR-20a plays a crucial role in maintaining the homeostasis of the thoracic aortic wall during TAD pathogenesis and may represent a potential therapeutic target for TAD.

Early evolution of the ecdysozoan body plan.

Extant ecdysozoans (moulting animals) are represented by a great variety of soft-bodied or articulated organisms that may or may not have appendages. However, controversies remain about the vermiform nature (i.e. elongated and tubular) of their ancestral body plan. We describe here Beretella spinosa gen. et sp. nov. a tiny (maximal length 3 mm) ecdysozoan from the lowermost Cambrian, Yanjiahe Formation, South China, characterized by an unusual sack-like appearance, single opening, and spiny ornament. Beretella spinosa gen. et sp. nov has no equivalent among animals, except Saccorhytus coronarius, also from the basal Cambrian. Phylogenetic analyses resolve both fossil species as a sister group (Saccorhytida) to all known Ecdysozoa, thus suggesting that ancestral ecdysozoans may have been non-vermiform animals. Saccorhytids are likely to represent an early off-shot along the stem-line Ecdysozoa. Although it became extinct during the Cambrian, this animal lineage provides precious insight into the early evolution of Ecdysozoa and the nature of the earliest representatives of the group.

[Vertical Differences in Grassland Bacterial Community Structure During Non- Growing Season in Eastern Ulansuhai Basin].

Grassland is an important part of the regional ecosystem, and its micro ecological structures play key roles in the process of element migration and the evolution of ecological diversity systems. To discover the spatial difference of the grassland soil bacterial community, we collected five total soil samples at 30 cm depth and 60 cm depth in Eastern Ulansuhai Basin in early May (before the beginning of the new growing season, with a minimum influence of human activities and other factors). Based on 16S rRNA gene-based high-throughput sequencing technology, the vertical characteristic of the bacterial community was analyzed in detail. First, Actinobacteriota, Proteobacteria, Chloroflexi, Acidobacteriota, Gemmatimonadota, Planctomycetota, Methylomirabilota, and Crenarchacota all appeared in the 30 cm and 60 cm samples, with the relative contents all being higher than 1%. In addition, there were a total of six phyla, five genera, and eight OTUs in the 60 cm sample with relative contents higher than those in the 30 cm sample. As a result, the relative abundance changes in dominant bacterial phyla, genera, and even OTUs at different sample depths did not correspond to their contribution to the bacterial community structure. Second, because of the unique contribution to the bacterial community structure in 30 cm and 60 cm samples, the norank_f__norank_o__norank_c__norank_p__Armatimonadota and Candidatus_Xiphinematobacter could be utilized as key bacterial genera during ecological system analysis, belonging to the Armatimonadota and Verrucomicrobiota, respectively. Finally, the relative abundances of ko00190, ko00910, and ko01200 were all higher in 60 cm samples than those in 30 cm samples, which showed that through the increase in metabolic function abundance, the relative contents of C, N, and P elements in grassland soil had been reduced with the increase in depth. These results will provide references for further study on the spatial change of bacterial communities in typical grassland.

Long-term outcomes after aortic valve surgery in patients with aortic regurgitation with preserved ejection fraction and left ventricular dilation.

OBJECTIVES: This study aims to assess the long-term outcomes and prognostic predictors of asymptomatic patients with severe aortic regurgitation (AR) accompanied by left ventricular ejection fraction (LVEF) ≥ 55% and left ventricular end-diastolic diameter (LVEDD) > 65 mm undergoing aortic valve replacement (AVR). METHODS: We retrospectively studied 291 consecutive asymptomatic patients with severe AR accompanied by LVEF ≥ 55% and LVEDD > 65 mm undergoing AVR from January 2000 to December 2013. The long-term outcomes and prognostic predictors were evaluated. RESULTS: There were 2 (0.7%) in-hospital deaths caused by multiple organ failure. The overall survival rate was 95.2% at 5 years, 89.9% at 10 years, 85.9% at 15 years, and 85.9% at 20 years. The left ventricular end-systolic volume index (LVESVi) was an independent predictor of overall mortality, with 59 ml/m2 being the best cut-off value. The left ventricular (LV) dimension decreased within 1 year after surgery and sustained thereafter. There were 15.5% of patients had incomplete LV reverse remodeling. LVESVi was an independent predictor of incomplete LV reverse remodeling, with 56 ml/m2 being the best cut-off value. CONCLUSIONS: AVR can be performed with an acceptable outcome in patients with severe AR accompanied by LVEF ≥ 55% and LVEDD > 65 mm. The LVESVi has the best predictive value for prognosis and the cut-off value is 59 ml/m2, and has the best predictive value for incomplete LV reverse remodeling and the cut-off value is 56 ml/m2.

Peptide derived from SLAMF1 prevents TLR4-mediated inflammation in vitro and in vivo.

Inflammation plays a crucial role in the development and progression of many diseases, and is often caused by dysregulation of signalling from pattern recognition receptors, such as TLRs. Inhibition of key protein-protein interactions is an attractive target for treating inflammation. Recently, we demonstrated that the signalling lymphocyte activation molecule family 1 (SLAMF1) positively regulates signalling downstream of TLR4 and identified the interaction interface between SLAMF1 and the TLR4 adaptor protein TRIF-related adapter molecule (TRAM). Based on these findings, we developed a SLAMF1-derived peptide, P7, which is linked to a cell-penetrating peptide for intracellular delivery. We found that P7 peptide inhibits the expression and secretion of IFNß and pro-inflammatory cytokines (TNF, IL-1ß, IL-6) induced by TLR4, and prevents death in mice subjected to LPS shock. The mechanism of action of P7 peptide is based on interference with several intracellular protein-protein interactions, including TRAM-SLAMF1, TRAM-Rab11FIP2, and TIRAP-MyD88 interactions. Overall, P7 peptide has a unique mode of action and demonstrates high efficacy in inhibiting TLR4-mediated signalling in vitro and in vivo.

Development of a multiple convolutional neural network-facilitated diagnostic screening program for immunofluorescence images of IgA nephropathy and idiopathic membranous nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) and idiopathic membranous nephropathy (IMN) are the most common glomerular diseases. Immunofluorescence (IF) tests of renal tissues are crucial for the diagnosis. We developed a multiple convolutional neural network (CNN)-facilitated diagnostic program to assist the IF diagnosis of IgAN and IMN. Methods: The diagnostic program consisted of four parts: a CNN trained as a glomeruli detection module, an IF intensity comparator, dual-CNN (D-CNN) trained as a deposition appearance and location classifier and a post-processing module. A total of 1573 glomerular IF images from 1009 patients with glomerular diseases were used for the training and validation of the diagnostic program. A total of 1610 images of 426 patients from different hospitals were used as test datasets. The performance of the diagnostic program was compared with nephropathologists. Results: In >90% of the tested images, the glomerulus location module achieved an intersection over union >0.8. The accuracy of the D-CNN in recognizing irregular granular mesangial deposition and fine granular deposition along the glomerular basement membrane was 96.1% and 93.3%, respectively. As for the diagnostic program, the accuracy, sensitivity and specificity of diagnosing suspected IgAN were 97.6%, 94.4% and 96.0%, respectively. The accuracy, sensitivity and specificity of diagnosing suspected IMN were 91.7%, 88.9% and 95.8%, respectively. The corresponding areas under the curve (AUCs) were 0.983 and 0.935. When tested with images from the outside hospital, the diagnostic program showed stable performance. The AUCs for diagnosing suspected IgAN and IMN were 0.972 and 0.948, respectively. Compared with inexperienced nephropathologists, the program showed better performance. Conclusion: The proposed diagnostic program could assist the IF diagnosis of IgAN and IMN.

Bayesian learners in gradient boosting for linear mixed models.

Selection of relevant fixed and random effects without prior choices made from possibly insufficient theory is important in mixed models. Inference with current boosting techniques suffers from biased estimates of random effects and the inflexibility of random effects selection. This paper proposes a new inference method "BayesBoost" that integrates a Bayesian learner into gradient boosting with simultaneous estimation and selection of fixed and random effects in linear mixed models. The method introduces a novel selection strategy for random effects, which allows for computationally fast selection of random slopes even in high-dimensional data structures. Additionally, the new method not only overcomes the shortcomings of Bayesian inference in giving precise and unambiguous guidelines for the selection of covariates by benefiting from boosting techniques, but also provides Bayesian ways to construct estimators for the precision of parameters such as variance components or credible intervals, which are not available in conventional boosting frameworks. The effectiveness of the new approach can be observed via simulation and in a real-world application.

Weighted envelope spectrum based on the spectral coherence for bearing diagnosis.

The key idea behind demodulation analysis for bearing diagnosis is to determine the fault-induced frequency band and directly detect the potential bearing fault characteristic frequency (FCF) in the demodulated spectrum. Till now, most demodulation methods are based on the optimal selection of only one informative frequency band. However, the unwanted in-band noise will be retained or some fault information may be ignored in the case of the discrete resonant frequency band or multiple informative frequency bands. To address the issue, a FCF-oriented criterion is proposed to determine all the informative frequency bands rather than only one specified frequency band. A new weighting vector is obtained to control the contribution of each spectral frequency in the demodulated spectrum. Subsequently, a weighted envelope spectrum (WES) is introduced by integrating the spectral correlation over the full spectral frequency band and assigning the new weighting vector on each spectral frequency. In this way, all frequency components with fault information are enhanced while other components are inhibited. Furthermore, expanded to the diagnosis of compound-fault, the FCF-oriented criterion can provide the different weighting vectors relevant to the different potential faults, and the separated fault features can be identified directly in the generated WESs. Finally, the advantages of WES over the traditional methods are testified by the simulated signal and experimental data.

Noninvasive preoperative differential diagnosis of gallbladder carcinoma and xanthogranulomatous cholecystitis: A retrospective cohort study of 240 patients.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an extremely rare entity. Due to XGC's clinical and radiological resemblance to gallbladder carcinoma (GBC), intraoperative frozen section during cholecystectomy is often performed to exclude the diagnosis of GBC. Our study is aiming to find a noninvasive indicator of XGC. To our knowledge, this is the largest XGC cohort ever studied. METHODS: This study retrospectively collected clinical characteristics, serological tests, and imaging features of 150 GBC patients and 90 XGC patients. The diagnosis of these 150 GBC patients and 90 XGC patients was based on intraoperative frozen section histopathology. T-test was utilized to compare differences between XGC and GBC. Receiver operating characteristic (ROC) curve was conducted and the area under the curve (AUC) was managed to evaluate the validity. RESULTS: The carcinoembryonic antigen (CEA) level in blood tests was significantly elevated in GBC patients than in XGC patients (p = 0.007). The presence of submucosal hypo-attenuated nodules (80% in XGC, 16% in GBC, p < 0.001), low density border (60% in XGC, 21% in GBC, p = 0.001), and nodular thickening in the bottom of the gallbladder with calcification (70% in XGC, 37% in GBC, p = 0.004) is significantly associated with XGC patients, whereas massive hilar infiltration (0% in XGC, 21% in GBC, p < 0.001), multiple lymph nodes in the hilar area (10% in XGC, 72% in GBC, p = 0.001), and gallbladder mucosal line continuity (50% in XGC, 95% in GBC, p = 0.002) are highly associated with GBC patients. The ROC curve was performed and the gallbladder mucosal line continuity (AUC = 0.708) and the AUC of low density border around the occupation (AUC = 0.654) showed a good prediction of XGC. CONCLUSIONS: Gallbladder mucosal line continuity and low density border around the occupation presented good indication value for the diagnosis of XGC. Our study proposed a noninvasive differential diagnosis method for XGC and GBC.

Low-Temperature Solution-Processed Cu2AgBiI6 Films for High Performance Photovoltaics and Photodetectors.

Recently, Cu2AgBiI6 semiconductor has been investigated due to the high absorption coefficient, direct bandgap, and low exciton binding energy, which are promising for eco-friendly photoelectric devices. Herein, pyridine is introduced as solvent additive to completely dissolve the solutes and form clear Cu2AgBiI6 precursor solution, which results in high-quality films and may provide a general approach for high-quality film growth of other bismuth-based metal halide semiconductors. In addition, the electronic structure of Cu2AgBiI6 has been demonstrated for the first time and shows an intrinsically weak n-type semiconductor. Furthermore, phenethylammonium iodide for surface passivation significantly improves the film quality, slightly n-dopes the material, and shifts up the band level. Finally, the photovoltaics and photodetector performance for n-i-p planar heterojunction devices have been investigated. The efficiency is up to 1%, highest for Cu2AgBiI6 solar cells and comparable with other lead-free bismuth based metal halide solar cells. Moreover, photodetectors with fast speed of rising and decaying time, especially the excellent specific photodetectivity of ∼1012 Jones within the wavelength of ∼350-600 nm, are achieved, which paves an alternative and promising strategy for the design of future commercial photodetectors that are self-powered, stable, nontoxic, etc.