Clinicopathological analysis of 18 cases of secretory carcinoma of the salivary glands.

Background/purpose: Secretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methods: Based on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. Results: Among the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. Conclusion: Combined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.

Merging Visible Light Photocatalysis and P(III)-Directed C-H Activation by a Single Catalyst: Modular Assembly of P-Alkyne Hybrid Ligands.

Metal-catalyzed C-H activation strategies provide an efficient approach for synthesis by minimizing atom, step, and redox economy. Developing milder, greener, and more effective protocols for these strategies is always highly desirable to the scientific community. In this study, the utilization of a single rhodium complex enabled the visible-light-induced late-stage C-H activation of biaryl-type phosphines with alkynyl bromides, employing inherent phosphorus atoms as directing groups. This chemistry combines P(III)-directed C-H activation with visible light photocatalysis, under exogenous photosensitizer-free conditions, offering a unique platform for ligand design and preparation. Furthermore, this study also explores the asymmetric catalysis and coordination chemistry of the resulting P-alkyne hybrid ligands with specific transition metals. Experimental results and density functional theory calculations demonstrate the mechanistic intricacies of this transformation.

Grip strength is an important predictor for nutritional risk and early postoperative ambulation in gastrointestinal tumors undergoing laparoscopic surgery: a prospective multicenter clinical study.

BACKGROUND: Using grip strength as a predictor of nutritional risk and early ambulation for gastrointestinal tumor surgery and determining its critical value have not been reported. This study was designed to explore the influencing factors of early postoperative ambulation ability for patients with gastrointestinal tumors who underwent laparoscopic surgery. METHODS: Four-hundred twenty-seven patients with gastrointestinal tumors who underwent laparoscopic surgery at three tertiary A hospitals in Beijing were prospectively enrolled. Subsequently, logistic regression analysis was conducted to determine the independent predictors of early postoperative ambulation. Logistic regression analyses for the different gender were also performed. In addition, the effectiveness of preoperative grip strength measurement in nutritional risk assessment was analyzed by using nutritional risk score 2002 (NRS 2002) as a control. RESULTS: The included cases were comprised of 283 male and 144 female patients, with an age of 59.35 ± 11.70 years. Gender, preoperative grip strength, operative time, and number of indwelling tubes were independent predictors of early postoperative ambulation. In the male group, lower preoperative grip strength and more indwelling tubes were independent risk factors for early postoperative ambulation. In the female group, lower preoperative grip strength and extended operating time were independent risk factors. Moreover, preoperative grip strength (male < 32 kg, female < 21 kg) can be used as a risk predictor for both preoperative nutritional risk and early postoperative ambulation. CONCLUSIONS: As a simple and objective measure of muscle strength, grip strength measurement is expected to be an effective predictor for both early postoperative ambulation ability and nutritional status of patients.

Bismuth-Catalyzed Amide Reduction.

In this article we report that a cationic version of Akiba's BiIII complex catalyzes the reduction of amides to amines using silane as hydride donor. The catalytic system features low catalyst loadings and mild conditions, en route to secondary and tertiary aryl- and alkylamines. The system tolerates functional groups such as alkene, ester, nitrile, furan and thiophene. Kinetic studies on the reaction mechanism result in the identification of a reaction network with an important product inhibition that is in agreement with the experimental reaction profiles.

A Near-Infrared-II Fluorescent Nanocatalyst for Enhanced CAR T Cell Therapy against Solid Tumor by Immune Reprogramming.

Chimeric antigen receptor (CAR) T cell therapy holds great promise in the treatment of hematological malignancies but performs poorly in solid tumors due to the tumor immunosuppressive microenvironment. Herein, a multifunctional nanocatalyst (APHA@CM) was prepared by encapsulating horseradish peroxidase (HRP)-loaded Au/polydopamine nanoparticles (Au/PDA NPs) and Ag2S quantum dots with CAR T cell membranes to improve the CAR T cell therapy in solid tumors. The APHA@CM has excellent multimodal imaging capability to precisely guide the scope and time window for nanocatalyst-induced tumor microenvironment regulation and CAR T cell therapy. The oxidase-like activity of Au NPs inhibited the glycolytic metabolism of tumor cells, reducing lactate efflux, reprogramming tumor immunosuppression, and ultimately increasing CAR T cell activation within the tumors. Additionally, the hypoxia environment of tumors could be relieved by HRP to enhance the Au/PDA NPs-induced synergistic sonodynamic/photothermal therapy (SDT/PTT), thereby promoting the immunogenic cell death of NALM 6 cells and enhancing CAR T cell-mediated immune microenvironment reprogramming. When this strategy was utilized to treat NALM 6 solid tumors, it not only completely eliminated tumors but also formed a long-term immune memory effect to inhibit tumor metastasis and recurrence. This work offers a strategy for CAR T cell therapy in solid tumor.

Synthesis, Isolation, and Characterization of Two Cationic Organobismuth(II) Pincer Complexes Relevant in Radical Redox Chemistry.

Herein, we report the synthesis, isolation, and characterization of two cationic organobismuth(II) compounds bearing N,C,N pincer frameworks, which model crucial intermediates in bismuth radical processes. X-ray crystallography uncovered a monomeric Bi(II) structure, while SQUID magnetometry in combination with NMR and EPR spectroscopy provides evidence for a paramagnetic S = 1/2 state. High-resolution multifrequency EPR at the X-, Q-, and W-band enable the precise assignment of the full g- and 209Bi A-tensors. Experimental data and DFT calculations reveal both complexes are metal-centered radicals with little delocalization onto the ligands.

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma.

BACKGROUND: Long-term outcome is unfavourable for relapsed/refractory (r/r) lymphoma patients who are resistant to salvage chemotherapy, even after subsequent autologous stem-cell transplantation (ASCT). Although anti-CD30 chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is relatively limited. METHODS: This open-label, single-center and single-arm pilot study investigated the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30+ lymphoma. The primary endpoint was safety and key secondary endpoint was overall response rate, overall survival, progression-free survival, and duration of response. RESULTS: Five classical Hodgkin lymphoma (cHL) patients and 1 anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) patient were enrolled. The median age was 24 years. No patient had prior ASCT. Three patients (50.0%) relapsed for ≥ 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) at enrollment. All patients received myeloablative chemotherapy and infused CD34-positive hematopoietic stem cells (HSCs) and CAR30 T cells in tandem, with a median dose of 3.9 × 106/kg and 7.6 × 106/kg, respectively. Five paitents presented with cytokine release syndrome (CRS), all of which were grade 1. No neurotoxicity was observed. All patients had successful HSCs engraftment and reached an objective response, including 5 (4 cHL and 1 ALCL, 83.3%) with a complete response (CR) and 1 with a partial response (PR). With a median follow-up of 20.4 (range, 12.1-34.4) months, all remained alive and maintained their responses. CONCLUSION: Our work demonstrates the combined administration of ASCT and CAR30 T-cell therapy is well-tolerate and highly effective in r/r cHL and ALCL, even in PET-positive or chemorefractory patients who are expected to have inferior outcome after ASCT, although further large-scaled validation in prospective clinical trial is warranted. Trial registration The trial was registered with the Chinese Clinical Trial Registry (ChiCTR, number ChiCTR2100053662).

Radical Activation of N-H and O-H Bonds at Bismuth(II).

The development of unconventional strategies for the activation of ammonia (NH3) and water (H2O) is of capital importance for the advancement of sustainable chemical strategies. Herein we provide the synthesis and characterization of a radical equilibrium complex based on bismuth featuring an extremely weak Bi-O bond, which permits the in situ generation of reactive Bi(II) species. The ensuing organobismuth(II) engages with various amines and alcohols and exerts an unprecedented effect onto the X-H bond, leading to low BDFEX-H. As a result, radical activation of various N-H and O-H bonds─including ammonia and water─occurs in seconds at room temperature, delivering well-defined Bi(III)-amido and -alkoxy complexes. Moreover, we demonstrate that the resulting Bi(III)-N complexes engage in a unique reactivity pattern with the triad of H+, H-, and H• sources, thus providing alternative pathways for main group chemistry.

Adalimumab for the treatment of cardiac sarcoidosis with multiple arrhythmias.

A 45-year-old male with cardiac sarcoidosis verified by cardiac biopsy presented with multiple coexisting arrhythmias, including ventricular tachycardia of more than 1000 episodes per 24 h, paroxysmal atrial fibrillation, and third-degree atrioventricular block. He did not respond to corticosteroids dose of 20-60 mg once daily and mycophenolate mofetil dose of 1 g twice daily for 6 months. Cardiac magnetic resonance (CMR) demonstrated inflammation and late gadolinium enhancement on right ventricular wall and interventricular septum. Positron emission tomography-computed tomography (PET-CT) showed multifocal 18 F-fluorodeoxyglucose uptake in the heart. We replaced mycophenolate mofetil with adalimumab, a tumour necrosis factor-α inhibitor. After 3 months, his arrhythmias improved significantly, manifesting as premature ventricular contractions of only 500 beats per 24 h and first-degree atrioventricular block. CMR showed a significant reduction in inflammation and late gadolinium enhancement, and PET-CT showed a complete resolution of fluorodeoxyglucose uptake.

DNA-Modified Liquid Crystal Droplets.

In this work, we have combined the advantages of sequence programmability of DNA nanotechnology and optical birefringence of liquid crystals (LCs). Herein, DNA amphiphiles were adsorbed onto LC droplets. A unique phenomenon of LC droplet aggregation was demonstrated, using DNA-modified LC droplets, through complementary DNA hybridization. Further functionalization of DNA-modified LC droplets with a desired DNA sequence was used to detect a wide range of chemicals and biomolecules, such as Hg2+, thrombin, and enzymes, through LC droplet aggregation and vice versa, which can be seen through the naked eye. These DNA-modified LC droplets can be printed onto a desired patterned surface with temperature-induced responsiveness and reversibility. Overall, our work is the first to report DNA-modified LC droplet, which provides a general detection platform based on the development of DNA aptamers. Additionally, this work inspires the exploration of surface information visualization combined with microcontact printing.

RNA methylation-mediated LINC01559 suppresses colorectal cancer progression by regulating the miR-106b-5p/PTEN axis.

Long noncoding RNAs (lncRNAs) regulate multiple biological effects in cancers. Recently, RNA methylation has been found to modify not only coding RNAs but also some noncoding RNAs. How RNA methylation affects lncRNAs to affect colorectal cancer (CRC) progression remains elusive. The expression of LINC01559 was explored through RNA sequencing, quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). The preliminary exploration of its function was performed using Western blotting (WB) and immunohistochemistry (IHC). Functional experiments in vitro and in vivo were conducted to explore the biological functions of LINC01559 in CRC. The LINC01559/miR-106-5p/PTEN axis was verified through fluorescence in situ hybridization (FISH), luciferase assays, and rescue experiments. RIP-sequencing, m6A RNA immunoprecipitation (MeRIP) assays and bioinformatic analysis were conducted to determine the upstream mechanism of LINC01559. The results showed that LINC01559 was downregulated in CRC compared with normal controls. Lower expression of LINC01559 in CRC patients predicted a poor prognosis. In addition, PTEN was found to be positively correlated with LINC01559, and miR-106b-5p could be the link between LINC01559 and PTEN. Then, silencing LINC01559 restored the malignant phenotype of CRC cells, while cotransfection of miR-106b-5p inhibitor neutralized this effect. Mechanistically, we found abundant m6A modification sites on LINC01559. Then, we uncovered these sites as potential targets of METTL3 through experiments in vivo. The results revealed a negative functional regulation of the LINC01559/miR-106b-5p/PTEN axis in CRC progression and explored a new mechanism of METTL3-mediated m6A modification on LINC01559. These results elucidate a novel potential therapeutic target for CRC treatment.

Combination of liquid crystal and deep learning reveals distinct signatures of Parkinson's disease-related wild-type α-synuclein and six pathogenic mutants.

α-Synuclein is a central player in Parkinson's disease (PD) pathology. Various point mutations in α-synuclein have been identified to alter the protein-phospholipid binding behavior and cause PD. Therefore, exploration of α-synuclein-phospholipid interaction is important for understanding the PD pathogenesis and helping the early diagnosis of PD. Herein, a phospholipid-decorated liquid crystal (LC)-aqueous interface is constructed to investigate the binding between α-synucleins (wild-type and six familial mutant A30P, E46K, H50Q, G51D, A53E and A53T) and phospholipid. The application of deep learning analyzes and reveals distinct LC signatures generated by the binding of α-synuclein and phospholipid. This system allows for the identification of single point mutant α-synucleins with an average accuracy of 98.3±1.3% in a fast and efficient manner. We propose that this analytical methodology provides a new platform to understand α-synuclein-lipid interactions, and can be potentially developed for easy identification of α-synuclein mutations in common clinic.

Simple and Rapid Detection of Ibuprofen─A Typical Pharmaceuticals and Personal Care Products─by a Liquid Crystal Aptasensor.

This work established a liquid crystal (LC) aptasensor for simple and rapid detection of ibuprofen, a typical pharmaceuticals and personal care products (PPCPs) pollutant. A negatively charged DNA aptamer specific for ibuprofen and a positively charged amphiphilic surfactant, hexadecyltrimethylammonium bromide (CTAB), were incubated with the sample and then directly added onto the LC interface. In the presence of ibuprofen, the specific binding of ibuprofen with the DNA aptamer will release CTAB, which then adsorbed at the LC-aqueous interface and induced the orientational change of LCs to homeotropic orientation with a dark optical signal output. While in the absence of ibuprofen, the DNA aptamer binds with CTAB through hydrophobic and electrostatic interactions, LCs remained in the planar orientation with a bright optical signal output. This LC aptasensor also has good specificity for ibuprofen and can even detect ibuprofen drug in tap water. Moreover, the response time of the LC aptasensor is fast in minutes. Additionally, this LC aptasensor benefits in monitoring the water quality and inspires the exploration of a general platform for PPCPs detection.

REPORT-Mild encephalitis/encephalopathy with a reversible splenial lesion associated with mumps infection: A case report.

We describe for the first time an child who demonstrated Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) after mumps infection in China. In this report, a 12-year-old boy came to Children's Hospital Affiliated to Zhengzhou University due to fever, swelling and pain under the earlobe for 4 days, and headache and vomiting for half of a day. Laboratory examinations showed a blood sodium level of 125mmol/L, both the Immunoglobulin M and Polymerase Chain Reaction results for the serum mumps virus were positive. Brain Magnetic Resonance Imaging (MRI) showed slight hypointense on T1 weighted images, hyperintense on T2-weighted images, fluid attenuated inversion recovery, diffusion-weighted images in the splenium of the corpus callosum indicative of MERS. On the 8th day, the patient no longer had swelling and pain around the parotid salivary glands, the sodium levels returned to normal. Onset of 14th d, follow-up brain MRI did not reveal any abnormalities. The case given to us indicates that MERS should be considered when patients after mumps infection presents with neurological symptoms and MRI should be performed to evaluate the splenium of the corpus callosum.

Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment.

In recent years, an increasing number of studies have reported that intestinal microbiota have an important effect on tumour immunity by affecting the tumour microenvironment (TME). The intestinal microbiota are closely associated with various immune cells, such as T lymphocytes, natural killer cells (NK cells) and macrophages. Some bacteria, such as Akkermansia muciniphila (A. muciniphila) and Lactobacillus reuteri (L. reuteri), have been shown to improve the effect of tumour immunity. Furthermore, microbial imbalance, such as the increased abundance of Fusobacterium nucleatum (F. nucleatum) and Helicobacter hepaticus (H. hepaticus), generally causes tumour formation and progression. In addition, some microbiota also play important roles in tumour immunotherapy, especially PD-L1-related therapies. Therefore, what is the relationship between these processes and how do they affect each other? In this review, we summarize the interactions and corresponding mechanisms among the intestinal microbiota, immune system and TME to facilitate the research and development of new targeted drugs and provide new approaches to tumour therapy.

Simple, rapid and sensitive detection of Parkinson's disease related alpha-synuclein using a DNA aptamer assisted liquid crystal biosensor.

Alpha-synuclein (αS) has been proposed as a potential biomarker for the diagnosis of Parkinson's disease (PD). However, the detection of αS using a simple, rapid and sensitive approach is still challenging. Herein, we construct a new type of biosensor for the detection of αS, combining the stimuli-responsiveness of liquid crystals (LCs) and the specific interaction of a DNA aptamer with proteins. In principle, the positively charged surfactant hexadecyltrimethylammonium bromide (CTAB) binds with the negatively charged DNA aptamer via electrostatic interactions; in the presence of αS, the DNA aptamer specifically binds with αS and releases CTAB, which is an amphiphilic molecule and subsequently assembles at the LC-aqueous interface, resulting in a homeotropic alignment of LCs with a dark optical signal. In the absence of αS, CTAB binds with the DNA aptamer without affecting the alignment of LCs, which shows planar anchoring with a bright optical signal. The response time of LCs towards αS is rapid and can be down to minutes. The LC biosensor established here has a good specificity for αS and can recognize αS even from a mixture of proteins. The LC biosensor also exhibits high sensitivity with a limit of detection of αS as low as 10 pM, which is comparable to that of the enzyme-linked immunosorbent assay. This work provides a new strategy for the detection of αS in a simple, rapid and sensitive manner, possessing promising potentials towards early diagnosis and clinical applications.

N6-methyladenosine-induced circ1662 promotes metastasis of colorectal cancer by accelerating YAP1 nuclear localization.

Tumor metastasis is the leading cause of death in patients with colorectal cancer (CRC). Circular RNAs (circRNAs) have been shown to be involved in cancer progression. However, the regulatory mechanisms of circRNAs involved in CRC tumor metastasis are currently unknown. Methods: High-throughput sequencing was performed on 6 pairs of CRC and adjacent normal tissues to identify the expression profiles of mRNA and circRNA. circ1662 was assessed by RNA-ISH and IHC of a tissue chip. The function of circ1662 in CRC was evaluated by knocking down or overexpressing circ1662. MeRIP-qPCR, RIP-qPCR, and RNA pull-down were performed to determine the relationship between METTL3, circ1662, and YAP1. Results: A novel circRNA, circ1662, exhibited significantly higher expression in CRC tissues than paired normal tissues. High circ1662 expression was correlated with poor prognosis and tumor depth in patients with CRC. Functionally, circ1662 promoted CRC cell invasion and migration by controlling EMT in vitro and in vivo. Mechanistically, circ1662 directly bound to YAP1 and accelerated its nuclear accumulation to regulate the SMAD3 pathway. Additionally, circ1662 enhanced CRC invasion and migration depending on YAP1 and SMAD3. Interestingly, METTL3 induced circ1662 expression by binding its flanking sequences and installing m6A modifications. Clinically, circ1662 expression strongly correlated with METTL3 and YAP1 protein expression. Moreover, YAP1 expression was negatively correlated with SMAD3 expression. Conclusions: METTL3-induced circ1662 promoted CRC cell invasion and migration by accelerating YAP1 nuclear transport. This result implies that circ1662 is a new prognostic and therapeutic marker for CRC metastasis.

Immune Landscape Refines the Classification of Colorectal Cancer With Heterogeneous Prognosis, Tumor Microenvironment and Distinct Sensitivity to Frontline Therapies.

The immune microenvironment has profound impacts on the initiation and progression of colorectal cancer (CRC). Therefore, the goal of this article is to identify two robust immune subtypes in CRC, further provide novel insights for the underlying mechanisms and clinical management. In this study, two CRC immune subtypes were identified using the consensus clustering of immune-related gene expression profiles in the meta-GEO dataset (n = 1,198), and their reproducibility was further verified in the TCGA-CRC dataset (n = 638). Subsequently, we characterized the immune escape mechanisms, gene alterations, and clinical features of two immune subtypes. Cluster 1 (C1) was defined as the "immune cold subtype" with immune cell depletion and deficiency, while cluster 2 (C2) was designed as the "immune hot subtype", with abundant immune cell infiltration and matrix activation. We also underlined the potential immune escape mechanisms: lack of MHC molecules and defective tumor antigen presentation capacity in C1, increased immunosuppressive molecules in C2. The prognosis and sensitivity to 5-FU, Cisplatin and immunotherapy differed between two subtypes. According to the two immune subtypes, we developed a prognosis associated risk score (PARS) with the accurate performance for predicting the prognosis. Additionally, two nomograms for overall survival (OS) and disease-free survival (DFS) were further constructed to facilitate clinical management. Overall, our research provides new references and insights for understanding and refining the CRC.

GSDME maintains hematopoietic stem cells by balancing pyroptosis and apoptosis.

GSDME contains a pore-forming domain at its N-terminal region to execute pyroptosis. Our previous study has reported that forced expression of Gsdme impairs the reconstitution capacity of hematopoietic stem cells (HSCs). While, how GSDME-mediated pyroptosis regulates HSCs remains unknown. Here, we show that hematopoietic stem and progenitor cells are capable to undergo pyroptosis in response to cisplatin treatment and GSDME is one of the genes mediating such process. Gsdme -/- mice revealed no difference in the steady state of blood system while Gsdme -/- HSCs exhibited compromised reconstitution capacity due to increased apoptosis. Briefly, this study reveals that GSDME modulates HSC function by coordinating pyroptosis and apoptosis.

[Basaloid squamous cell carcinoma in gingiva: a case report].

As an aggressive subtype of squamous cell carcinoma, basaloid squamous cell carcinoma (BSCC) rarely occurs in the oral and maxillofacial region. The gingiva is an unusual site of BSCC. This study reported a 78-year-old male who presented with left maxillary pain. Clinical examination revealed a gingival mass in the left maxilla. Under microscope, the lesion showed typical comedo necrosis and peripheral palisading. Areas of glandular-like structures were also observed. Immunohistochemistry results revealed that the Ki-67 score of BSCC in this case was 28%, and S-100 was positive in some areas. However, P16 and CK7 were negative. Finally, a diagnosis of BSCC was made based on the pathological and immunohistochemical characteristics. The patient underwent subtotal maxillectomy. After 12 months later, the patient was alive with no evidence of disease. Combined with relevant literature, this article analyzed the clinicopathological features, differential diagnosis, diagnosis, treatment, and prognosis of BSCC. Although surgery remains the main treatment in the head and neck region, radiation-chemotherapy should be considered in some human papilloma virus-positive cases.