Intercage Polymerization of Postfunctionalized Phosphine Organic Prisms into Cage-Based Assemblies with Tunable Morphologies.

Great effort has been dedicated to the engineering of porous organic cages (POCs) in geometry and topology. Yet, harnessing these cage-like entities as premade building units to construct infinite cage-based superstructures remains elusive. In this study, we design a type of vertex-modified phosphine organic prism by a postfunctionalized approach and use it as a ditopic cage monomer to achieve an intercage supramolecular polymerization via the synergy of metal coordination and π-π dimerization. The resulting cage-by-cage polymers can further hierarchically organize into superstructures of diverse morphologies and dimensionalities, including 1D fibers, 2D lamellae, and 3D vesicles. Control over the cosolvents is capable of well regulating their structural hierarchies and self-assembled shapes. This would pave a way for the creation of cage-based supramolecular assemblies and nanomaterials.

Gas-Responsive and Gas-Releasing Polymer Assemblies.

In order to explore the unique physiological roles of gas signaling molecules and gasotransmitters in vivo, chemists have engineered a variety of gas-responsive polymers that can monitor their changes in cellular milieu, and gas-releasing polymers that can orchestrate the release of gases. These have advanced their potential applications in the field of bio-imaging, nanodelivery, and theranostics. Since these polymers are of different chain structures and properties, the morphology of their assemblies will manifest distinct transitions after responding to gas or releasing gas. In this review, we summarize the fundamental design rationale of gas-responsive and gas-releasing polymers in structure and their controlled transition in self-assembled morphology and function, as well as present some perspectives in this prosperous field. Emerging challenges faced for the future research are also discussed.

High-fidelity single logical qubit encoding scheme assisted by single-sided quantum dot-cavity systems.

We present an encoding scheme of a single logical qubit with single-sided quantum dot (QD)-cavity systems, which is immune to the collective decoherence. By adjusting the Purcell factor to satisfy the balanced reflection condition, the detrimental effects of unbalanced reflection between the coupled and uncoupled QD-cavity systems can be effectively suppressed. Furthermore, the fidelity of each step can be increased to unity regardless of the strong coupling regime and the weak coupling regime of cavity quantum electrodynamics (QED) with the assistance of waveform correctors. The scheme requires QD-cavity systems and simple linear optical elements, which can be implemented with the currently experimental techniques.

A reference profile of N-glycosylation for human kidney and the identification of cell-cell interactions between parietal epithelial cells and capillary endothelial cells by single-cell glycosylation-sequencing.

Background N-glycosylation is one of the most common post-translational modifications in humans, and these alterations are associated with kidney diseases. Methods A novel technological approach, single-cell N-acetyllactosamine sequencing (scLacNAc-seq), was applied to simultaneously detect N-glycosylation expression and the transcriptome at single-cell resolution in three human kidney tissues from zero-time biopsy. Cell clusters, glycation abundance in each cell cluster, functional enrichment analysis, cell-cell crosstalk, and Pseudotime analysis were applied. Results Using scLacNAc-seq, 24,247 cells and 22 cell clusters were identified, and N-glycan abundance in each cell was obtained. Transcriptome analysis revealed a close connection between capillary endothelial cells (CapECs) and parietal epithelial cells (PECs). PECs and CapECs communicate with each other through several pairs of ligand receptors (e.g., TGFB1-EGFR, GRN-EGFR, TIMP1-FGFR2, VEGFB-FLT1, ANGPT2-TEK, and GRN-TNFRSF1A). Finally, a regulatory network of cell-cell crosstalk between PECs and CapECs was constructed, which is involved in cell development. Conclusions We here, for the first time, constructed the glycosylation profile of 22 cell clusters in the human kidney from time-zero biopsy. Moreover, cell-cell communication between PECs and CapECs through the ligand-receptor system may play a crucial regulatory role in cell proliferation.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Cinnamaldehyde: An effective component of Cinnamomum cassia inhibiting Helicobacter pylori.

ETHNOPHARMACOLOGICAL RELEVANCE: Cinnamomum cassia Presl (Cinnamomum cassia) is a common traditional Chinese medicine, which can promote the secretion and digestion of gastric juice, improve the function of gastrointestinal tract. Cinnamaldehyde (CA) is a synthetic food flavoring in the Chinese Pharmacopoeia. AIM OF THE STUDY: This study aimed to search for the active ingredient (CA) of inhibiting H. pylori from Cinnamomum cassia, and elucidate mechanism of action, so as to provide the experimental basis for the treatment of H. pylori infection with Cinnamomum cassia. MATERIALS AND METHODS: It's in vitro and in vivo pharmacological properties were evaluated based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and an acute gastric inflammation model in mice infected with H. pylori. Drug safety was evaluated using the CCK8 method and high-dose administration in mice. The advantageous characteristics of CA in inhibiting H. pylori were confirmed using acidic conditions and in combination with the antibiotics. The mechanism underlying the action of CA on H. pylori was explored using scanning electron microscopy (SEM), adhesion experiments, biofilm inhibition tests, ATP and ROS release experiments, and drug affinity responsive target stability (DARTS) screening of target proteins. The protein function and target genes were verified by molecular docking and Real-Time quantitative reverse transcription PCR (qRT-PCR). RESULTS: The results demonstrated that CA was found to be the main active ingredient against H. pylori in Cinnamomum cassia in-vitro tests, with a MIC of 8-16 µg/mL. Moreover, CA effectively inhibited both sensitive and resistant H. pylori strains. The dual therapy of PPI + CA exhibited remarkable in vivo efficacy in the acute gastritis mouse model, superior to the standard triple therapy. DARTS, molecular docking, and qRT-PCR results suggested that the target sites of action were closely associated with GyrA, GyrB, AtpA, and TopA, which made DNA replication and transcription impossible, then leading to inhibition of bacterial adhesion and colonization, suppression of biofilm formation, and inhibition ATP and enhancing ROS. CONCLUSIONS: This study demonstrated the suitability of CA as a promising lead drug against H. pylori, The main mechanisms can target GyrA ect, leading to reduce ATP and produce ROS, which induces the apoptosis of bacterial.

Accumulation of docosapentaenoic acid (n-3 DPA) in a novel isolate of the marine ichthyosporean Sphaeroforma arctica.

OBJECTIVE: Currently, there is lack of a consistent and highly enriched source for docosapentaenoic acid (n-3 DPA, C22:5), and this work report the isolation of microorganism that naturally produces n-3 DPA. RESULTS: In this work, we screened microorganisms in our culture collections with the goal to isolate a strain with high levels of n-3 DPA. We isolated a strain of Sphaeroforma arctica that produces up to 11% n-3 DPA in total fatty acid and has a high n-3 DPA to DHA/EPA ratio. The cell growth of the isolated strain was characterized using microscopy imaging and flow cytometer technologies to confirm the coenocytic pattern of cell divisions previously described in S. arctica. Our novel isolate of S. arctica grew more robustly and produced significantly more n-3 DPA compared to previously isolated and described strains indicating the uniqueness of the discovered strain. CONCLUSION: Overall, this work reports a first isolate n-3 DPA producing microorganism and establishes the foundation for future strain improvement and elucidation of the physiological function of this LC-PUFA for human nutrition and health.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Digital PCR for Single-Cell Analysis.

Single-cell analysis provides an overwhelming strategy for revealing cellular heterogeneity and new perspectives for understanding the biological function and disease mechanism. Moreover, it promotes the basic and clinical research in many fields at a single-cell resolution. A digital polymerase chain reaction (dPCR) is an absolute quantitative analysis technology with high sensitivity and precision for DNA/RNA or protein. With the development of microfluidic technology, digital PCR has been used to achieve absolute quantification of single-cell gene expression and single-cell proteins. For single-cell specific-gene or -protein detection, digital PCR has shown great advantages. So, this review will introduce the significance and process of single-cell analysis, including single-cell isolation, single-cell lysis, and single-cell detection methods, mainly focusing on the microfluidic single-cell digital PCR technology and its biological application at a single-cell level. The challenges and opportunities for the development of single-cell digital PCR are also discussed.

Engineering Dual CO2- and Photothermal-Responsive Membranes for Switchable Double Emulsion Separation.

Stimulus-responsive membranes demonstrate promising applications in switchable oil/water emulsion separations. However, they are unsuitable for the treatment of double emulsions like oil-in-water-in-oil (O/W/O) and water-in-oil-in-water (W/O/W) emulsions. For efficient separation of these complicated emulsions, fine control over the wettability, response time, and aperture structure of the membrane is required. Herein, dual-coated fibers consisting of primary photothermal-responsive and secondary CO2-responsive coatings are prepared by two steps. Automated weaving of these fibers produces membranes with photothermal- and CO2-responsive characteristics and narrow pore size distributions. These membranes exhibit fast switching wettability between superhydrophilicity (under CO2 stimulation) and high hydrophobicity (under near-infrared stimulation), achieving on-demand separation of various O/W/O and W/O/W emulsions with separation efficiencies exceeding 99.6%. Two-dimensional low-field nuclear magnetic resonance and correlated spectra technique are used to clarify the underlying mechanism of switchable double emulsion separation. The approach can effectively address the challenges associated with the use of stimulus-responsive membranes for double emulsion separation and facilitate the industrial application of these membranes.

Influence of the brain­gut axis on neuroinflammation in cerebral ischemia­reperfusion injury (Review).

Stroke, a debilitating cerebrovascular ailment, poses significant threats to human life and health. The intricate interplay between the gut­brain­microbiota axis (GBMA) and cerebral ischemia­reperfusion has increasingly become a focal point of scientific exploration, emerging as a pivotal research avenue in stroke pathophysiology. In the present review, the authors delved into the nexus between the GBMA and neuroinflammation observed post­stroke. The analysis underscored the pivotal roles of histone deacetylase 3 and neutrophil extracellular traps subsequent to stroke incidents. The influence of gut microbial compositions and their metabolites, notably short­chain fatty acids and trimethylamine N­oxide, on neuroinflammatory processes, was further elucidated. The involvement of immune cells, especially regulatory T­cells, and the intricate signaling cascades including cyclic GMP­AMP synthase/stimulator of interferon genes/Toll­like receptor, further emphasized the complex regulatory mechanisms of GBMA in cerebral ischemia/reperfusion injury (CI/RI). Collectively, the present review offered a comprehensive perspective on the metabolic, immune and inflammatory modulations orchestrated by GBMA, augmenting the understanding of its role in neuroinflammation following CI/RI.

Access to N-Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction.

N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.

Clinical Effect of Vitamin E Combined with Recombinant Human Epidermal Growth Factor on the Recurrent Oral Ulcer and Effects of Serum Superoxide Dismutase, IL-10, and TNF-α.

Objective: To examine the therapeutic effects of vitamin E combined with recombinant human epidermal growth factor on recurrent oral ulcers as well as on the levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor- (TNF-α), to provide evidence to facilitate medical management. Method: From June 2021 to May 2022, 84 patients with recurrent oral ulcers assessed and treated in our hospital were assigned to the control group and observation group with 42 cases in each group. Vitamin E was administered to the control group, while recombinant human epidermal growth factor and vitamin E were administered to the observation group. The clinical efficacy, serum SOD level, inflammatory factor level (IL-10, TNF-α), immune function index, clinical symptom improvement, pain disappearance time, healing time of ulcer surface, and adverse reactions were examined. Results: Clinical efficacy of the observation group (92.86%) was considerably greater than the control group (73.81%), (P < .05). Following treatment, the observation group had comparatively higher levels of serum SOD and significantly decreased TNF-α and IL-10 concentrations compared to the control group (P < .05). Similarly, post-treatment, the observation group had substantially higher CD3+, CD4+, and CD4+/CD8+ concentrations and lower CD8+ concentrations compared to the normal control (P < .05). In contrast to the control group, the observation group's pain degree score, ulcer diameter, duration for pain relief, and ulcer surface healing time duration were reduced substantially (P < .05). Notably, the incidence of adverse reactions was fairly similar in both groups (P > .05). Conclusion: Vitamin E combined with recombinant human epidermal growth factor has a significant clinical effect on recurrent oral ulcers, can achieve rapid improvement of symptoms in patients, and is relatively safe to be used as a clinical therapy.

Optimizing hepatocellular carcinoma disease staging systems by incorporating tumor micronecrosis: A multi-institutional retrospective study.

Tumor micronecrosis is a pathological feature that reflects malignant biological behavior in hepatocellular carcinoma (HCC). However, whether micronecrosis can optimize HCC staging systems remains unilluminated. A total of 1632 HCC patients who underwent curative hepatectomy in four institutions from January 2014 to December 2021 were enrolled in this study. Independent prognostic factors were identified, and optimized staging models were established using a training cohort (n = 934). The performance of optimized staging models was validated using an external cohort consisting of cases from three other institutions (n = 232). In addition, patients from our prospectively collected database (n = 379) tested the application effectiveness of the models. Harrel's c-statistics and the corrected Akaike information criterion (AICc) were used to assess the performance of staging models. In most of Barcelona Clinic Liver Cancer (BCLC) and tumor (T) stages, HCC patients with tumor micronecrosis showed poorer prognosis than those without. Tumor micronecrosis, microvascular invasion, multiple tumors and tumor size >2 cm were independent prognostic-related factors. The BCLC and T staging models incorporating tumor micronecrosis showed better performance than the original systems (c-statistic, 0.712 and 0.711 vs. 0.664 and 0.679; AICc, 2314.8 and 2322.3 vs. 2338.2 and 2338.1; respectively). Furthermore, the external validation cohort confirmed that the optimized staging models had improved efficiency compared with the original ones. Moreover, the prospective cohort demonstrated the applicability of the optimized staging systems. Tumor micronecrosis plays a stage-ascending role in HCC patients. The BCLC and T staging systems incorporating tumor micronecrosis can improve the prognosis stratification efficiency of patients.

Recent advances in combatting bacterial infections via well-designed metallacycles/metallacages.

Bacterial infections can lead to the development of large-scale outbreaks of diseases that pose a serious threat to human life and health. Also, conventional antibiotics are prone to producing resistance and allergic reactions, and their therapeutic effect is dramatically diminished when bacterial communities form biofilms. Fortunately, well-designed supramolecular coordination complexes (SCCs) have been used as antibacterials or anti-biofilms in recent years. SCCs can kill bacteria by directly engaging with the bacterial surface through electrostatic interactions or by penetrating the bacterial membrane through the auxiliary effect of cell-penetrating peptides. Furthermore, scientists have engineered fluorescent SCCs that can produce reactive oxygen species (ROS) to eliminate bacteria when exposed to laser irradiation, and they also demonstrate outstanding performance in in vivo imaging, enabling integrated diagnosis and treatment. In this review, we summarize the design strategy and applications of SCCs in antibacterials or anti-biofilms and provide an outlook on future research.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

Impact of prognostic nutritional index change on prognosis after colorectal cancer surgery under propofol or sevoflurane anesthesia.

BACKGROUND: The alteration of the prognostic nutritional index (PNI) or the utilization of distinct anesthesia strategies has been linked to the prognosis of various cancer types, but the existing evidence is limited and inconclusive, particularly for colorectal cancer (CRC). Our objective was to evaluate the association between PNI change and progression free survival (PFS) and overall survival (OS) in patients treated with CRC surgery after propofol-based or sevoflurane-based anesthesia. METHODS: We conducted a retrospective analysis of 414 patients with CRC who underwent surgical resection. Among them, 165 patients received propofol-based total intravenous anesthesia (TIVA-P), while 249 patients received sevoflurane-based inhalation anesthesia (IA-S). The PNI change (ΔPNI) was calculated by subtracting the pre-surgery PNI from the post-surgery PNI, and patients were categorized into high (≥ -2.25) and low (< -2.25) ΔPNI groups. Univariate and multivariate analyses were employed to evaluate the effects of the two anesthesia methods, ΔPNI, and their potential interaction on PFS and OS. RESULTS: The median duration of follow-up was 35.9 months (interquartile range: 18-60 months). The five-year OS rates were 63.0% in the TIVA-P group and 59.8% in the IA-S group (hazard ratio [HR]: 0.96; 95% confidence interval [CI]: 0.70-1.35; p = 0.864), while the five-year PFS rates were 55.8% and 51.0% (HR: 0.92; 95% CI: 0.68-1.26; p = 0.614), respectively. In comparison to patients in the low ΔPNI group, those in the high ΔPNI group exhibited a favorable association with both OS (HR: 0.57; 95% CI: 0.40-0.76; p < 0.001) and PFS (HR: 0.58; 95% CI: 0.43-0.79; p < 0.001). Stratified analysis based on ΔPNI revealed significant protective effects in the propofol-treated participants within the high ΔPNI group, whereas such effects were not observed in the low ΔPNI group, for both OS (p for interaction = 0.004) and PFS (p for interaction = 0.024). CONCLUSIONS: Our data revealed that among patients who underwent CRC surgery, those treated with TIVA-P exhibited superior survival outcomes compared to those who received IA-S, particularly among individuals with a high degree of PNI change.

Regulating Tumorigenicity and Cancer Metastasis through TRKA Signaling.

Tropomyosin receptor kinase (TRK) A, TRKA, is a specific binding receptor of nerve growth factor (NGF), which plays an essential role in the occurrence and progression of human cancers. TRKA overexpression has been proven to be a powerful carcinogenic driver and has been verified in many tumors. The TRKA receptor kinase domain is over-activated in an NGF-dependent manner, accompanied by activation of downstream signal pathways, such as RAS-MAPK, PI3K-AKT, JAK2-STAT3 pathway, PLC γ pathway, and Hippo pathway, which participate in tumor cell proliferation, invasion, epithelial-mesenchymal transition (EMT), perineural invasion (PNI), drug resistance, and cancer pain. In addition, chimeric oncogenes produced by the fusion of NTRK1 and other genes are also the direct cause of tumorigenesis and cancer development. The newly developed TRK inhibitors can improve symptoms and tumor regression in cancer patients with overexpression of TRKA or NTRK1 fusion gene. With the emergence of drug resistance, next generation of TRK inhibitors can still maintain strong clinical efficacy in the case of TRK kinase domain mutations, and these inhibitors are in clinical trials. This review summarizes the characteristics and research progress of TRKA, focusing on the regulatory role of the TRKA signal pathway in different tumors. In addition, we have summarized the clinical significance of TRKA and the TRK inhibitors. This review may provide a new reference for the study of the mechanism of TRKA in different tumors, and also provide a new perspective for the in-depth understanding of the role of TRKA as a biomarker and therapeutic target in human cancer.