Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma.

Background: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma. Case presentation: A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor. Conclusion: It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Systemic Thrombolysis for Isolated Splenic Vein Thrombosis Secondary to Oral Contraceptives: A Case Report.

Isolated splenic vein thrombosis (ISVT) is a very rare venous thromboembolism in the absence of pancreatic diseases, which can cause acute abdominal pain and chronic left-side portal hypertension. Herein, we reported a 40-year-old female patient who developed ISVT after taking oral contraceptives. Anticoagulation with oral rivaroxaban was the first-line choice of therapy in this case. Since then, abdominal pain alleviated, but she did not achieve vessel recanalization. Thus, a 7-day systemic thrombolysis with urokinase was given. Abdominal pain disappeared, but ISVT was not significantly improved. During follow-up period, long-term anticoagulation with oral rivaroxaban was given. Collectively, this case indicates the possibility of oral contraceptives as a risk factor of ISVT as well as anticoagulation combined with systemic thrombolysis as a choice of treatment for ISVT. Certainly, long-term follow-up is necessary in this case.

Expression of concern: A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma.

Expression of concern for 'A hypoxia-dissociable siRNA nanoplatform for synergistically enhanced chemo-radiotherapy of glioblastoma' by Yandong Xie, et al., Biomater. Sci., 2022, 10, 6791-6803, https://doi.org/10.1039/D2BM01145J.

Rational Design of the Spatial Effect in a Fe(II)/α-Ketoglutarate-Dependent Dioxygenase Reverses the Regioselectivity of C(sp3)-H Bond Hydroxylation in Aliphatic Amino Acids.

The hydroxylation of remote C(sp3)-H bonds in aliphatic amino acids yields crucial precursors for the synthesis of high-value compounds. However, accurate regulation of the regioselectivity of remote C(sp3)-H bonds hydroxylation in aliphatic amino acids continues to be a common challenge in chemosynthesis and biosynthesis. In this study, the Fe(II)/α-ketoglutarate-dependent dioxygenase from Bacillus subtilis (BlAH) was mined and found to catalyze hydroxylation at the γ and δ sites of aliphatic amino acids. Through crystal structure analysis, molecular dynamic simulation and quantum chemical calculations revealed that regioselectivity was regulated by the spatial effect of BlAH. Based on this result, the spatial effect of BlAH was reconstructed to stabilize the transition state at the δ site of aliphatic amino acids, thereby successfully reversing the γ site regioselectivity to the δ site. For example, the regioselectivity of L-Homoleucine (5a) was reversed from the γ site (1:12) to the δ site (>99:1). The present study not only expands the toolbox of biocatalysts for the regioselective functionalization of remote C(sp3)-H bonds, but also provides a theoretical guidance for the precision-driven modification of similarly remote C(sp3)-H bonds in complex molecules.

Improvement in the Sustained-Release Performance of Electrospun Zein Nanofibers via Crosslinking Using Glutaraldehyde Vapors.

Volatile active ingredients in biopolymer nanofibers are prone to burst and uncontrolled release. In this study, we used electrospinning and crosslinking to design a new sustained-release active packaging containing zein and eugenol (EU). Vapor-phase glutaraldehyde (GTA) was used as the crosslinker. Characterization of the crosslinked zein nanofibers was conducted via scanning electron microscopy (SEM), mechanical properties, water resistance, and Fourier transform infrared (FT-IR) spectroscopy. It was observed that crosslinked zein nanofibers did not lose their fiber shape, but the diameter of the fibers increased. By increasing the crosslink time, the mechanical properties and water resistance of the crosslinked zein nanofibers were greatly improved. The FT-IR results demonstrated the formation of chemical bonds between free amino groups in zein molecules and aldehyde groups in GTA molecules. EU was added to the zein nanofibers, and the corresponding release behavior in PBS was investigated using the dialysis membrane method. With an increase in crosslink time, the release rate of EU from crosslinked zein nanofibers decreased. This study demonstrates the potential of crosslinking by GTA vapors on the controlled release of the zein encapsulation structure containing EU. Such sustainable-release nanofibers have promising potential for the design of fortified foods or as active and smart food packaging.

Commonly used software tools produce conflicting and overly-optimistic AUPRC values.

The precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.

Optical-Helicity-Dependent Orbital and Spin Dynamics in Two-Dimensional Ferromagnets.

Disentangling orbital (OAM) and spin (SAM) angular momenta in the ultrafast spin dynamics of two-dimensional (2D) ferromagnets on subfemtoseconds is a challenge in the field of ultrafast magnetism. Herein, we employed a non-collinear spin version of real-time time-dependent density functional theory to investigate the orbital and spin dynamics of the 2D ferromagnets Fe3GeTe2 (FGT) induced by circularly polarized light. Our results show that the demagnetization of the Fe sublattice in FGT is accompanied by helicity-dependent precession of the OAM and SAM excited by circularly polarized lasers. We further identify that precession of the OAM and SAM in FGT is faster than demagnetization within a few femtoseconds. Remarkably, circularly polarized lasers can significantly induce a periodic transverse linear response of the OAM and SAM on very ultrafast time scales of ∼600 attoseconds. Our finding suggests a powerful new route for attosecond regimes of the angular momentum manipulation to coherently control helicity-dependent orbital and spin dynamics in 2D ferromagnets.

Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress ß-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

BACKGROUND: The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). METHODS: This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. RESULTS: The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). CONCLUSION: HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Case report: Rapid development of acute symptomatic portal vein system thrombosis after endoscopic variceal therapy in a patient with liver cirrhosis.

Acute portal vein thrombosis (PVST), a serious complication of liver cirrhosis, is characterized as abdominal pain secondary to intestinal ischemia, and even intestinal necrosis. Anticoagulation is recommended for the treatment of acute PVST, but is often postponed in cirrhotic patients with acute variceal bleeding or those at a high risk of variceal bleeding. Herein, we reported a 63-year-old male with a 14-year history of alcoholic liver cirrhosis who developed progressive abdominal pain related to acute portal vein and superior mesenteric vein thrombosis immediately after endoscopic variceal ligation combined with endoscopic cyanoacrylate glue injection for acute variceal bleeding. Fortunately, acute PVST was successfully recanalized by the use of low molecular weight heparin. Collectively, this case suggests that acute symptomatic PVST can be secondary to endoscopic variceal therapy in liver cirrhosis, and can be safely and successfully treated by anticoagulation.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation.

OBJECTIVE: Increasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH). METHODS: A total of 383 patients (aged 24-76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors. RESULTS: Among the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05). CONCLUSION: In patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

Melatonin enhances resistance to Botryosphaeria dothidea in pear by promoting jasmonic acid and phlorizin biosynthesis.

Ring rot, caused by Botryosphaeria dothidea, is an important fungal disease of pear fruit during postharvest storage. Melatonin, as a plant growth regulator, plays an important role in enhancing the stress resistance of pear fruits. It enhances the resistance of pear fruits to ring rot by enhancing their antioxidant capacity. However, the underlying mechanism remains unclear. In this study, we examined the effect of melatonin on the growth of B. dothidea. Results showed that melatonin did not limit the growth of B. dothidea during in vitro culture. However, metabolomics and transcriptomics analyses of 'Whangkeumbae' pear (Pyrus pyrifolia) revealed that melatonin increased the activity of antioxidant enzymes, including peroxidase (POD), superoxide dismutase (SOD), and polyphenol oxidase (PPO), in the fruit and activated the phenylpropanoid metabolic pathway to improve fruit resistance. Furthermore, melatonin treatment significantly increased the contents of jasmonic acid and phlorizin in pear fruit, both of which could improve disease resistance. Jasmonic acid regulates melatonin synthesis and can also promote phlorizin synthesis, ultimately improving the resistance of pear fruit to ring rot. In summary, the interaction between melatonin and jasmonic acid and phlorizin enhances the antioxidant defense response and phenylpropanoid metabolism pathway of pear fruit, thereby enhancing the resistance of pear fruit to ring rot disease. Our results provide new insights into the application of melatonin in the resistance to pear fruit ring rot.

Pyrrole-containing hybrids as potential anticancer agents: An insight into current developments and structure-activity relationships.

Cancer poses a significant threat to human health. Therefore, it is urgent to develop potent anti-cancer drugs with excellent inhibitory activity and no toxic side effects. Pyrrole and its derivatives are privileged heterocyclic compounds with significant diverse pharmacological effects. These compounds can target various aspects of cancer cells and have been applied in clinical settings or are undergoing clinical trials. As a result, pyrrole has emerged as a promising drug scaffold and has been further probed to get novel entities for the treatment of cancer. This article reviews recent research progress on anti-cancer drugs containing pyrrole. It focuses on the mechanism of action, biological activity, and structure-activity relationships of pyrrole derivatives, aiming to assist in designing and synthesizing innovative pyrrole-based anti-cancer compounds.

Dual-Message QR Codes.

A novel dual-message QR code is proposed for carrying two individual messages that can be read by standard QR code readers: one from a close range and the other from a large distance. By exploring the module value determining the rule of typical QR code readers, we designed two-state module blocks that can be recognized as different module values through changing the distance from which the QR code is scanned, and applied them to construct the proposed dual-message QR code. Experiments were conducted to test the readability of the two messages within a dual-message QR code, with the results demonstrating the high feasibility of the proposed method. The dual-message QR code can be applied for designing creative applications. For example, an interactive wedding card that can access the growing film of the groom and that of the bride interchangeably, which bring the viewers a higher-quality experience.

Tetraniliprole risk assessment: Unveiling a hidden threat for managing a generalist herbivore.

Insecticide resistance poses a significant challenge in managing generalist herbivores such as the tobacco cutworm (TCW), Spodoptera litura. This study investigates the potential risks associated with using the novel diamide insecticide tetraniliprole to control TCW. A tetraniliprole-resistant strain was developed through twelve generations of laboratory selection, indicating an intermediate risk of resistance development. Field monitoring in China revealed a significant incidence of resistance, particularly in the Nanchang (NC) population (>100-fold). Tetraniliprole showed moderate to high cross-resistance to multiple insecticides and was autosomally inherited with incomplete dominance, controlled by multiple genes, some of which belong to the cytochrome P450 family associated with enhanced detoxification. Life table studies indicated transgenerational hormesis, stimulating TCW female fecundity and increasing population net reproduction rates (R0). These findings suggest a potential for pest resurgence under tetraniliprole use. The integrated risk assessment provides a basis for the sustainable management of TCW using tetraniliprole.

Childhood maltreatment and personality disorders in adolescents and adults with psychotic or non-psychotic disorders.

Introduction: While the attention to personality disorders (PD) and childhood maltreatment (CM) has grown in recent years, there remains limited understanding of the prevalence and distinctions of PD and CM in clinical populations of Chinese adolescents in comparison to adults. Methods: A total of 1,417 participants were consecutively sampled from patients diagnosed with either psychotic or non-psychotic disorders in the psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. The participants were categorized into two groups based on their age: adolescents (aged 15-21 years) and adults (aged 22-35 years). PDs were evaluated using a self-reported personality diagnostic questionnaire and a structured clinical interview, while CMs were assessed using the Chinese version of the Child Trauma Questionnaire Short Form. Results: When comparing self-reported PD traits and CM between adolescents and adults, differences emerge. Adolescents, particularly in the psychotic disorder group, exhibit more pronounced schizotypal PD traits (p=0.029), and this pattern extends to non-psychotic disorders (p<0.001). Adolescents in the non-psychotic disorder group also report higher levels of emotional abuse (p=0.014), with a notable trend in physical abuse experiences compared to adults (p=0.057). Furthermore, the most prevalent PDs in the clinical sample are avoidant, borderline, and obsessive-compulsive PDs. Among patients with psychotic disorders, adolescents exhibit higher rates of schizoid, schizotypal, and obsessive-compulsive PDs compared to adults. Logistic regression analyses highlight distinct predictors for psychotic and non-psychotic disorders in adolescents and adults. Discussion: The findings emphasize distinct differences in PDs and CMs between adolescent and adult groups, shedding light on their potential roles in psychotic and non-psychotic disorders.

Subject-Agnostic Transformer-Based Neural Speech Decoding from Surface and Depth Electrode Signals.

Objective: This study investigates speech decoding from neural signals captured by intracranial electrodes. Most prior works can only work with electrodes on a 2D grid (i.e., Electrocorticographic or ECoG array) and data from a single patient. We aim to design a deep-learning model architecture that can accommodate both surface (ECoG) and depth (stereotactic EEG or sEEG) electrodes. The architecture should allow training on data from multiple participants with large variability in electrode placements and the trained model should perform well on participants unseen during training. Approach: We propose a novel transformer-based model architecture named SwinTW that can work with arbitrarily positioned electrodes, by leveraging their 3D locations on the cortex rather than their positions on a 2D grid. We train both subject-specific models using data from a single participant as well as multi-patient models exploiting data from multiple participants. Main Results: The subject-specific models using only low-density 8x8 ECoG data achieved high decoding Pearson Correlation Coefficient with ground truth spectrogram (PCC=0.817), over N=43 participants, outperforming our prior convolutional ResNet model and the 3D Swin transformer model. Incorporating additional strip, depth, and grid electrodes available in each participant (N=39) led to further improvement (PCC=0.838). For participants with only sEEG electrodes (N=9), subject-specific models still enjoy comparable performance with an average PCC=0.798. The multi-subject models achieved high performance on unseen participants, with an average PCC=0.765 in leave-one-out cross-validation. Significance: The proposed SwinTW decoder enables future speech neuroprostheses to utilize any electrode placement that is clinically optimal or feasible for a particular participant, including using only depth electrodes, which are more routinely implanted in chronic neurosurgical procedures. Importantly, the generalizability of the multi-patient models suggests the exciting possibility of developing speech neuroprostheses for people with speech disability without relying on their own neural data for training, which is not always feasible.