Genome-wide identification and expression analysis of phytochrome-interacting factor genes during abiotic stress responses and secondary metabolism in the tea plant.

Phytochrome-interacting factors (PIFs) are pivotal transcriptional regulators controlling photomorphogenesis, environmental responses, and development in plants. However, their specific roles in coordinating adaptation towards abiotic stress and metabolism remain underexplored in tea plants. Here, we identified seven PIF members from four distinct clades (PIF1, PIF3, PIF7, and PIF8). Promoter analysis implicated CsPIFs in integrating light, stress, hormone, and circadian signals. Most CsPIFs exhibited rapid increase in expression under shading, especially CsPIF7b/8a, which displayed significant changes in long-term shading condition. Under drought/salt stress, CsPIF3b emerged as a potential positive regulator. CsPIF3a was induced by low temperature and co-expressed with CsCBF1/3 and CsDREB2A cold response factors. Dual-luciferase assays confirmed that act as negative regulator of the CBF pathway. Expression profiling across 11 tea cultivars associated specific CsPIFs with chlorophyll biosynthesis and accumulation of anthocyanins, flavonols, and other metabolites. In summary, this study highlights the significance of CsPIFs as central coordinators in managing intricate transcriptional reactions to simultaneous abiotic stresses and metabolic adjustments in tea plants. This insight informs future strategies for enhancing this economically crucial crop through crop improvement initiatives.

Increased ONECUT2 induced by Helicobacter pylori promotes gastric cancer cell stemness via an AKT-related pathway.

Helicobacter pylori (HP) infection initiates and promotes gastric carcinogenesis. ONECUT2 shows promise for tumor diagnosis, prognosis, and treatment. This study explored ONECUT2's role and the specific mechanism underlying HP infection-associated gastric carcinogenesis to suggest a basis for targeting ONECUT2 as a therapeutic strategy for gastric cancer (GC). Multidimensional data supported an association between ONECUT2, HP infection, and GC pathogenesis. HP infection upregulated ONECUT2 transcriptional activity via NFκB. In vitro and in vivo experiments demonstrated that ONECUT2 increased the stemness of GC cells. ONECUT2 was also shown to inhibit PPP2R4 transcription, resulting in reduced PP2A activity, which in turn increased AKT/ß-catenin phosphorylation. AKT/ß-catenin phosphorylation facilitates ß-catenin translocation to the nucleus, initiating transcription of downstream stemness-associated genes in GC cells. HP infection upregulated the reduction of AKT and ß-catenin phosphorylation triggered by ONECUT2 downregulation via ONECUT2 induction. Clinical survival analysis indicated that high ONECUT2 expression may indicate poor prognosis in GC. This study highlights a critical role played by ONECUT2 in promoting HP infection-associated GC by enhancing cell stemness through the PPP2R4/AKT/ß-catenin signaling pathway. These findings suggest promising therapeutic strategies and potential targets for GC treatment.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Recent progress in Surface-Enhanced Raman Spectroscopy detection of biomarkers in liquid biopsy for breast cancer.

Breast cancer is the most commonly diagnosed cancer in women globally and a leading cause of cancer-related mortality. However, current detection methods, such as X-rays, ultrasound, CT scans, MRI, and mammography, have their limitations. Recently, with the advancements in precision medicine and technologies like artificial intelligence, liquid biopsy, specifically utilizing Surface-Enhanced Raman Spectroscopy (SERS), has emerged as a promising approach to detect breast cancer. Liquid biopsy, as a minimally invasive technique, can provide a temporal reflection of breast cancer occurrence and progression, along with a spatial representation of overall tumor information. SERS has been extensively employed for biomarker detection, owing to its numerous advantages such as high sensitivity, minimal sample requirements, strong multi-detection ability, and controllable background interference. This paper presents a comprehensive review of the latest research on the application of SERS in the detection of breast cancer biomarkers, including exosomes, circulating tumor cells (CTCs), miRNA, proteins and others. The aim of this review is to provide valuable insights into the potential of SERS technology for early breast cancer diagnosis.

Hybrid Local and Charge-Transfer Material with Ultralong Room Temperature Phosphorescence for Efficient Organic Afterglow Light-Emitting Diodes.

Organic ultralong room temperature phosphorescence (OURTP) materials capable of combining various emission behaviors for diversified optoelectronic properties and applications have recently gained a vigorous development, but it remains a forbidden challenge in designing OURTP molecules with hybrid local and charge-transfer (HLCT) feature, possibly due to the elevated difficulties in simultaneously meeting the stringent requirements of both HLCT and OURTP emitters. Here, through introducing multiple heteroatoms into one-dimensional fused ring of coumarin with moderate charge transfer perturbation in donor-π-acceptor architecture, we demonstrate a HLCT-featured OURTP molecule showing both promoted fluorescence with a quantum yield of 77% in solution and long-lived OURTP with a lifetime of 251 ms in conventional host material used in electroluminescent device. Thus, efficient OURTP organic light-emitting diodes (OLEDs) were fabricated, exhibiting bright electroluminescence with an exciton utilization efficiency of 85% and yellow OURTP lasting over 2 s for afterglow. Impressively, the HLCT OURTP-OLEDs can be further optimized to reach an unprecedented total external quantum efficiency (EQE) of ~12% and OURTP EQE up to 3.11%, representing the highest performance among the reported OURTP-OLEDs. These impressive results highlight the significance to fuse HLCT and OURTP together in enriching OURTP materials and improving the afterglow OLED performances.

Seafood intake in childhood/adolescence and the risk of obesity: results from a Nationwide Cohort Study.

BACKGROUND & AIMS: Obesity has been linked to various detrimental health consequences. While there is established evidence of a negative correlation between seafood consumption and obesity in adults, the current research on the association between seafood intake in childhood/adolescence and the risk of obesity is lacking. Our aim was to evaluate the association between seafood intake in childhood/adolescence and the risk of obesity in a Chinese nationwide cohort. METHODS: We utilized data from the China Health and Nutrition Survey (CHNS) from the year of 1997 to 2015. Seafood consumption was evaluated through 3-day 24-hour recalls. In our study, overweight/obesity status was determined based on the Chinese Criteria of Overweight and Obesity in School-age Children and Adolescents (WS/T 586-2018), while abdominal obesity status was determined according to the Chinese Criteria of Waist Circumference Screening Threshold among Children and Adolescents (WS/T 611-2018). RESULTS: During an average follow-up of 7.9 years, 404 cases developed overweight/obesity among 2206 participants in the seafood-overweight/obesity analysis, while 381 cases developed abdominal obesity among 2256 participants in the seafood-abdominal-obesity analysis. The high-consumer group was associated with 35% lower risk of overweight/obesity risk and 26% lower risk of abdominal obesity after fully adjusting for sociodemographic and lifestyle factors, compared with the non-consumer group. Considering different cooking methods, boiled seafood consumption was associated with 43% lower risk of overweight/obesity and 23% lower risk of abdominal obesity in the fully adjusted model, while stir-fried seafood did not demonstrate a statistical significance. CONCLUSION: Higher intake of seafood in childhood/adolescents, particularly in a boiled way, was associated with lower obesity risk.

Surface activation via selective dealloying of Cu-based metallic glasses for efficient catalytic behavior.

Surface activation is considered to regulate the electronic structures of materials for enhancing catalytic capability. Herein, we report a controllable strategy for constructing three-dimensional micro-nanoporous copper catalysts with high reactivity and activity for the degradation reaction of organic pollutants. Various micro-nanoporous structures and in situ formation processes by chemical selective dealloying of Cu-based metallic glasses are evaluated due to the surface modification. The porous catalysts exhibit superior catalytic performance, attributing to the catalytic mechanisms related to the superior surface activity of nanoscale copper composites and the strong oxidizing capability of activated radicals. These findings will provide a promising synthesis approach for three-dimensional micro-nanoporous catalysts for many chemical reactions.

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: The authors aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR ≤0.4, and sLNR >0.4. Patients in the D2+No. 10 group were randomly divided into the training ( n =302) and validation ( n =130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate, and high SHLN metastasis burden groups (LMB, MMB, and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) ( P <0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Deep learning-based 3D quantitative total tumor burden predicts early recurrence of BCLC A and B HCC after resection.

OBJECTIVES: This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm3) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses. RESULTS: A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC An stage; whilst the BCLC B high-TTB patients remained in a BCLC Bn stage. The 2-year ER rate was 30.5% for BCLC An patients vs. 58.1% for BCLC Bn patients (HR = 2.8; p < 0.001). CONCLUSIONS: TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B. CLINICAL RELEVANCE STATEMENT: Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy. KEY POINTS: Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients.

A chromosome-level genome assembly for the paramylon-producing microalga Euglena gracilis.

Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Raman spectroscopy: A promising analytical tool used in human reproductive medicine.

Over the past few years, there has been growing interest in developing new methods of embryo quality assessment to improve the outcomes of assisted reproductive technologies in the medical field. Raman microscopy as an increasingly promising analytical tool has been widely used in life sciences, biomedicine and "omics" to study molecular, biochemical components, living cells and tissues due to the label-free and non-destructive nature of the imaging technique. This paper reviews the analytical capability of Raman microscopy and applications of Raman spectroscopy technology mainly in reproductive medicine. The purpose of this review is to introduce the Raman spectroscopy technology, application and underlying principles of the method, to provide an intact picture of its uses in biomedical science and reproductive medicine, to offer ideas for its future application, verification and validation. The focus is on the application of Raman spectroscopy in the reproductive medicine field, including the application in gametes, embryos and spent embryo culture media.

Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Radiotherapy for patients with locally advanced esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy combined with chemotherapy.

With the success of immunotherapy in advanced esophageal cancer, neoadjuvant chemo-immunotherapy (CIT) is being increasingly used for local staged esophageal cancer, especially in the context of clinical trials, which brings similar pCR with neoadjuvant chemoradiotherapy and shows promising results. However, there is still a part of potentially operable patients can't undergo surgery after neoadjuvant chemo-immunotherapy. The follow-up treatment and prognosis of this population remain unclear. Patients pathologically diagnosed with ESCC, clinical stage T1-3N+M0 or T3-4aNanyM0 (AJCC 8th), PS 0-1 were retrospectively enrolled from 1/2020 to 6/2021 in Zhejiang Cancer Hospital. All patients firstly received PD-1 inhibitors plus chemotherapy (albumin paclitaxel, 260 mg/m2 on day 1 plus carboplatin AUC = 5 on day 1) every 3 weeks for 2-4 cycles. For those patients who did not receive surgery, definitive radiotherapy with 50.4 Gy/28F or 50 Gy/25F was adopted using VMAT, concurrent with chemotherapy or alone. The concurrent chemotherapy regimens included weekly TC (paclitaxel 50 mg/m2, d1, carboplatin AUC = 2, d1) or S1 (60 mg bid d1-14, 29-42). The survival outcomes and treatment toxicity were recorded and analyzed. A total of 56 eligible patients were finally identified from 558 patients who were treated in department of thoracic surgery, among all the patients, 25 (44.6%) received radiotherapy alone, and 31 (55.4%) received chemoradiotherapy after neoadjuvant CIT. The median follow-up was 20.4 months (interquartile range [IQR] 8.7-27 months). The median PFS and OS were 17.9 months (95% confidence interval [CI] 11.0-21.9 months) and 20.5 months (95% CI 11.8-27.9 months), respectively. In the subgroup analysis, the median OS was 26.3 months (95% CI 15.33-NA) for patients exhibiting partial response (PR) to CIT, compared to 17 months (95% CI 8.77-26.4) for those with stable disease (SD) or progressive disease (PD), yielding a hazard ratio (HR) of 0.54 (95% CI 0.27-1.06, P = 0.07). No significant difference was observed for patients received radiotherapy alone or chemoradiotherapy with HR = 0.73 (95% CI 0.72-2.6, P = 0.33). The most common Adverse events (AEs) observed during this study were anemia (98.2%), leukopenia (83.9%), thrombocytopenia (53.6%). AEs of grade ≥ 3 radiation-induced pneumonitis and esophagitis were 12.5% and 32.1%, especially, 6 patients (10.7%) died from esophageal fistula and 2 patients (3.6%) died from grade 5 pneumonitis. For local advanced ESCC patients after neoadjuvant CIT who did not receive surgery, definitive radiotherapy was an optional treatment strategy. However, those patients with no response to CIT also showed poor response to radiotherapy, and particular attention should be paid to treatment related toxicity, especially esophageal fistula.

Contrast enhancement boost improves the image quality of CT angiography derived from 80-kVp cerebral CT perfusion data.

RATIONALE AND OBJECTIVE: To investigate the impact of the contrast enhancement boost (CE-boost) technique on the image quality of CT angiography (CTA) derived from 80-kVp cerebral CT perfusion (CTP) data, and to compare it with conventional CTApeak as well as other currently employed methods for enhancing CTA images, such as CTAtMIP and CTAtAve extracted from CTP. MATERIALS AND METHODS: The data of forty-seven patients who underwent CTP at 80 kVp were retrospectively collected. Four sets of images: CTApeak, CTAtMIP, CTAtAve, and CE-boost images. The CTApeak image represents the arterial phase at its peak value, captured as a single time point. CTAtMIP and CTAtAve are 4D CTA images that provide maximum density projection and average images from the three most prominent time points. CE-boost is a postprocessing technique used to enhance contrast in the arterial phase at its peak value. We compared the average CT value, standard deviation (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the internal carotid artery (ICA) and basilar artery (BA) among the four groups. Image quality was evaluated using a 5-point scale. RESULTS: The CE-boost demonstrated and CNR in the ICA and BA (all p < 0.001). Compared with the other three CTA reconstructed images, the CE-boost images had the best subjective image quality, with the highest scores of 4.77 ± 0.43 and 4.87 ± 0.34 for each reader (all p < 0.001). CONCLUSION: Compared with other currently used techniques,CE-boost enhances the image quality of CTA derived from 80-kVp CTP data, leading to improved visualization of intracranial arteries.

An experimental study on flow behaviour in suction filling of pharmaceutical powders.

Die filling is a crucial step in the pharmaceutical tablet manufacturing process. For industrial-scale production using rotary presses, suction filling is typically employed due to its significant efficiency advantages over gravity filling. Despite its widespread use, our understanding of the suction filling process remains limited. Specifically, there is insufficient comprehension of how filling performance is influenced by factors such as suction velocity, filling velocity, and the properties of the powder materials. Building on our previous research, this study aims to further investigate the effects of powder properties and process parameters (e.g., filling velocity, suction velocity, fill depth) on suction filling behaviour. A systematic experimental investigation was conducted using a model suction filling system, considering both cohesive and free-flowing pharmaceutical powders. The effect of fill depth on the suction filling of these powders was examined at different filling and suction velocities. The results demonstrate that two distinctive flow regimes in suction filling can be identified: slow filling and fast filling. These regimes are delineated by a critical filling-to-suction velocity ratio. In the slow filling regime, the filling-to-suction velocity ratio is lower than the critical ratio, meaning that the filling phase is slower than the suction phase. Conversely, the fast filling regime occurs when the filling-to-suction velocity ratio exceeds the critical ratio, implying that the filling phase is faster than the suction phase. This study reveals, for the first time, that when the powder flow pattern during suction filling is dominated by plug flow, full die fill (i.e., the fill ratio equals unity) is achieved in the slow filling regime. However, in the fast filling regime, incomplete die fill is obtained. It is also found that when plug flow prevails during fast filling, the fill ratio has an inverse correlation with the filling-to-suction velocity ratio. This study further reveals that when the plug flow assumption is valid, the filling ratio at various fill-to-suction velocity ratios can be well predicted mathematically. Furthermore, it is also found that once the powder flow pattern differs from the ideal plug flow, which could be induced by the filling conditions and powder cohesion, the fill ratio can be overpredicted.

Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membrane-decorated nanoparticles.

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRPα on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

Electrophile-Arene Affinity: An Energy Scale for Evaluating the Thermodynamics of Electrophilic Dearomatization Reactions.

Rational design and development of organic reactions are lofty goals in synthetic chemistry. Quantitative description of the properties of molecules and reactions by physical organic parameters plays an important role in this regard. In this Article, we report an energy scale, namely, electrophile-arene affinity (EAA), for evaluating the thermodynamics of electrophilic dearomatization reactions, a class of important transformations that can rapidly build up molecular complexity and structural diversity by converting planar aromatic compounds into three-dimensional cyclic molecules. The acquisition of EAA data can be readily achieved by theoretically calculating the enthalpy changes (ΔH) of the hypothetical reactions of various (cationic) electrophiles with aromatic systems (taking the 1-methylnaphthalen-2-olate ion as an example in this study). Linear correlations are found between the calculated ΔH values and established physical organic parameters such as the percentage of buried volume %VBur (steric effect), Hammett's σ or Brown's σ+ (electronic effect), and Mayr's E (reaction kinetics). Careful analysis of the ΔH values leads to the rational design of a dearomative alkynylation reaction using alkynyl hypervalent iodonium reagents as the electrophiles.

Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Periductal Mastitis, a Disease with Distinct Clinicopathological Features from Granulomatous Lobular Mastitis.

Purpose: Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies. Patients and Methods: Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration. Results: PDM patients had a higher median age compared to GLM patients (38 vs 32, p<0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p<0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p<0.001), ductal wall thickening (47.93% vs 1.75%, p<0.001), and ductal rupture (44.63% vs 5.26%, p<0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p<0.001), microabscess (68.42% vs 28.93%, p<0.001), and lipid vacuole (40.35% vs 8.26%, p<0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy. Conclusion: PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.