Development of a chemiluminescence assay for tissue plasminogen activator inhibitor complex and its applicability to gastric cancer.

BACKGROUND: Venous thromboembolism (VTE), is a noteworthy complication in individuals with gastric cancer, but the current diagnosis and treatment methods lack accuracy. In this study, we developed a t-PAIC chemiluminescence kit and employed chemiluminescence to detect the tissue plasminogen activator inhibitor complex (t-PAIC), thrombin-antithrombin III complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC) and thrombomodulin (TM), combined with D-dimer and fibrin degradation products (FDP), to investigate their diagnostic potential for venous thrombosis in gastric cancer patients. The study assessed variations in six indicators among gastric cancer patients at different stages. RESULTS: The t-PAIC reagent showed LOD is 1.2 ng/mL and a linear factor R greater than 0.99. The reagents demonstrated accurate results, with all accuracy deviations being within 5%. The intra-batch and inter-batch CVs for the t-PAIC reagent were both within 8%. The correlation coefficient R between this method and Sysmex was 0.979. Gastric cancer patients exhibited elevated levels of TAT, PIC, TM, D-D, FDP compared to the healthy population, while no significant difference was observed in t-PAIC. In the staging of gastric cancer, patients in III-IV stages exhibit higher levels of the six markers compared to those in I-II stages. The ROC curve indicates an enhancement in sensitivity and specificity of the combined diagnosis of four or six indicators. CONCLUSION: Our chemiluminescence assay performs comparably to Sysmex's method and at a reduced cost. The use of multiple markers, including t-PAIC, TM, TAT, PIC, D-D, and FDP, is superior to the use of single markers for diagnosing VTE in patients with malignant tumors. Gastric cancer patients should be screened for the six markers to facilitate proactive prophylaxis, determine the most appropriate treatment timing, ameliorate their prognosis, decrease the occurrence of venous thrombosis and mortality, and extend their survival.

Inhibition of ROS/caspase-3/GSDME-mediated pyroptosis alleviates high glucose-induced injury in AML-12 cells.

Diabetic liver injury (DLI) is a chronic complication of the liver caused by diabetes, and its has become one of the main causes of nonalcoholic fatty liver disease (NAFLD). The gasdermin E (GSDME)-dependent pyroptosis signaling pathway is involved in various physiological and pathological processes; however, its role and mechanism in DLI are still unknown. This study was performed to investigate the role of GSDME-mediated pyroptosis in AML-12 cell injury induced by high glucose and to evaluate the therapeutic potential of caspase-3 inhibition for DLI. The results showed that high glucose activated apoptosis by regulating the apoptotic protein levels including Bax, Bcl-2, and enhanced cleavage of caspase-3 and PARP. Notably, some of the hepatocytes treated with high glucose became swollen, accompanied by GSDME-N generation, indicating that pyroptosis was further induced by active caspase-3. Moreover, the effects of high glucose on AML-12 cells could be partly reversed by a reactive oxygen scavenger (NAC) and caspase-3 specific inhibitor (Z-DEVD-FMK), which suggests high glucose induced GSDME-dependent pyroptosis in AML-12 cells through increasing ROS levels and activating caspase-3. In conclusion, our results show that high glucose can induce pyroptosis in AML-12 cells, at least in part, through the ROS/caspase-3/GSDME pathway，and inhibition of caspase-3 can ameliorate high glucose-induced hepatocyte injury, providing an important basis for clarifying the pathogenesis and treatment of DLI.

Acquired Fanconi syndrome in mixed cryoglobulinemia patients: a single-center case series.

PURPOSE: Cryoglobulinemia is a pathological condition characterized by the presence of cryoglobulins in the blood, with cryoglobulinemic glomerulonephritis being the most frequent form of renal involvement. Fanconi syndrome presents as a generalized dysfunction of the proximal tubule, characterized by the presence of polyuria, phosphaturia, glycosuria, proteinuria, proximal renal tubular acidosis, and osteomalacia. We aimed to present five cases co-occurring with Fanconi syndrome and cryoglobulinemia. METHODS: We retrospectively summarized the cases of five patients with Fanconi syndrome and cryoglobulinemia at Peking Union Medical College Hospital from January 2012 to June 2022. The clinical features, diagnosis, treatment, and prognosis were systematically analyzed. RESULTS: All five patients exhibited typical features of Fanconi syndrome, and cryoglobulinemia was concurrently detected in all cases. These patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, and IgM constitutes the predominant monoclonal component in cryoglobulins. In addition to supplemental treatment, timely immunosuppressive therapy may potentially benefit the long-term renal prognosis of patients with this condition. CONCLUSION: Our findings highlight the rare co-occurrence of Fanconi syndrome and cryoglobulinemia in clinical practice. Despite the lack of causal evidence, the coexistence of Fanconi syndrome and tubulointerstitial injury is also noteworthy in patients with cryoglobulinemia, underscoring the importance of thorough evaluation and tailored management in patients presenting with overlapping renal manifestations. Key Points • Patients with mixed cryoglobulinemia can clinically present with tubulointerstitial injury, specifically manifesting as Fanconi syndrome. • In addition to typical symptoms of Fanconi syndrome, these patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, while IgM constitutes the monoclonal component in cryoglobulins. • Timely immunosuppressive therapy may improve long-term renal prognosis in these patients.

Shikonin and chitosan-silver nanoparticles synergize against triple-negative breast cancer through RIPK3-triggered necroptotic immunogenic cell death.

Necroptotic immunogenic cell death (ICD) can activate the human immune system to treat the metastasis and recurrence of triple-negative breast cancer (TNBC). However, developing the necroptotic inducer and precisely delivering it to the tumor site is the key issue. Herein, we reported that the combination of shikonin (SHK) and chitosan silver nanoparticles (Chi-Ag NPs) effectively induced ICD by triggering necroptosis in 4T1 cells. Moreover, to address the lack of selectivity of drugs for in vivo application, we developed an MUC1 aptamer-targeted nanocomplex (MUC1@Chi-Ag@CPB@SHK, abbreviated as MUC1@ACS) for co-delivering SHK and Chi-Ag NPs. The accumulation of MUC1@ACS NPs at the tumor site showed a 6.02-fold increase compared to the free drug. Subsequently, upon reaching the tumor site, the acid-responsive release of SHK and Chi-Ag NPs from MUC1@ACS NPs cooperatively induced necroptosis in tumor cells by upregulating the expression of RIPK3, p-RIPK3, and tetrameric MLKL, thereby effectively triggering ICD. The sequential maturation of dendritic cells (DCs) subsequently enhanced the infiltration of CD8+ and CD4+ T cells in tumors, while inhibiting regulatory T cells (Treg cells), resulting in the effective treatment of primary and distal tumor growth and the inhibition of TNBC metastasis. This work highlights the importance of nanoparticles in mediating drug interactions during necroptotic ICD.

A novel sponge composite of chitosan-sodium tripolyphosphate-melamine for anionic dye Orange II removal.

Since the potential carcinogenic, toxic and non-degradable dyes trigger serious environmental contamination by improper treatment, developing novel adsorbents remains a major challenge. A novel high efficiency and biopolymer-based environmental-friendly adsorbent, chitosan­sodium tripolyphosphate-melamine sponge (CTS-STPP-MS) composite, was prepared for Orange II removing with chitosan as raw material, sodium tripolyphosphate as cross-linking agent. The composite was carefully characterized by SEM, EDS, FT-IR and XPS. The influence of crosslinking conditions, dosage, pH, initial concentration, contacting time and temperature on adsorption were tested through batch adsorption experiments. CTS-STPP-MS adsorption process was exothermic, spontaneous and agreed with Sips isotherm model accompanying the maximum adsorption capacity as 948 mg∙g-1 (pH = 3). Notably, the adsorption performance was outstanding for high concentration solutions, with a removal rate of 97 % in up to 2000 mg∙L-1 OII solution (100 mg sorbent dosage, 50 mL OII solution, pH = 3, 289.15 K). In addition, the adsorption efficiency yet remained 97.85 % after 5 repeated adsorption-desorption cycles. The driving force of adsorption was attributed to electrostatic attraction and hydrogen bonds which was proved by adsorption results coupled with XPS. Owing to the excellent properties of high-effective, environmental-friendly, easy to separate and regenerable, CTS-STPP-MS composite turned out to be a promising adsorbent in contamination treatment.

WDR61 ablation triggers R-loop accumulation and suppresses breast cancer progression.

Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.

Lighting ATR/Chk1 by mesoscale TopBP1 condensates.

Biomolecular condensation has gained considerable attention as a fundamental mechanism in cell signaling and various biological processes. A recent study by Egger et al. provides valuable insights into the constituents of topoisomerase IIß binding protein 1 (TopBP1) condensates and sheds light on the mechanism of Chk1 activation by ataxia telangiectasia-mutated and Rad3-related (ATR) at the interface of these condensates.

Comprehensive analysis of IGF2BP3 with expression features, prognosis, immune modulation and stemness in hepatocellular carcinoma and pan-cancer.

Insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) is a critical m6A reader. It encodes proteins that contain several KH domains, which are important in RNA binding, RNA synthesis and metabolism. Lots of researches have studied the malignant potential of m6A readers in tumors. However, the biological functional analysis of IGF2BP3 in hepatocellular carcinoma (HCC) and pan-cancer is not comprehensive. In this study, we used a bioinformatics approach to comprehensively analyze the significance of IGF2BP3 in HCC through analyzing its expression, mutation, prognosis, protein-protein interaction (PPI) network, functional enrichment, and the correlation with ferroptosis, stemness as well as immune modulation in HCC. IGF2BP3 presented a negative correlation with the ferroptosis molecule NFE2L2, and a positive correlation with the ferroptosis molecule SLC1A5 as well as the immune checkpoint HAVCR2. In addition, we also analyzed IGF2BP3 expression, prognosis and immune modulation in pan-cancer, revealing the prognostic value of IGF2BP3 in a variety of tumors. Finally, we verified the biological functions of IGF2BP3 in HCC through various experiments. The data showed that IGF2BP3 may enhance the proliferation, colony formation and invasion capacities of HCC cells, and IGF2BP3 is mainly positively correlated with the expression level of stemness marker SOX2. In conclusion, IGF2BP3 had a potential to be a new perspective biomarker in forecasting the immune response, ferroptosis, stemness and prognosis of HCC or even pan-cancer.

Clinical Value of Human Endogenous Retrovirus-H Long Terminal Repeat Associating 2 (HHLA2) in Small Cell Lung Cancer.

Objective: Human endogenous retrovirus-H long terminal repeat associating 2 (HHLA2) is a new immune checkpoint in the B7 family, and the value of HHLA2 in small cell lung cancer (SCLC) is unknown. Methods: We retrospectively detected HHLA2 expression by immunohistochemistry in SCLC patients. Moreover, plasma biomarkers of SCLC were detected retrospectively. Results: Seventy-four percent of SCLC patients exhibited HHLA2 expression. HHLA2 staining was localised within the nucleus of SCLC cells, while no staining was detected in normal lung tissue specimens. The correlation between HHLA2 expression and clinical factors was also analysed. Limited stage (LS) SCLC was more common than extensive stage (ES) SCLC among patients with HHLA2 staining. SCLC patients without metastasis had higher HHLA2 expression than SCLC patients with metastasis. HHLA2 expression was more frequently detected in the group with a tumour size greater than 5 cm than in the group with a tumour size less than 5 cm. The proportion of patients with HHLA2-positive staining was greater in the stage III and IV SCLC groups than in the stage I and II SCLC groups. A high proportion of SCLC patients with HHLA2-positive staining had a survival time <2 years. Neuron-specific enolase (NSE), CEA and Ki-67 levels were measured. The NSE level in the HHLA2-positive group was significantly greater than that in the HHLA2-negative group. The CEA and Ki-67 levels did not significantly differ between the HHLA2-positive and HHLA2-negative patients, nor were age, sex, smoking status, nodal metastasis status, Karnofsky Performance Scale (KPS) score, or Ki-67 expression score. HHLA2-positive SCLC patients had higher tumour stages and shorter 2-year survival times than HHLA2-negative patients did. Conclusion: The new immune molecule HHLA2 may be an ideal clinical biomarker for predicting SCLC progression and could serve as a new immunotherapy target in SCLC.

Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex.

Chronic pain is a complex disease. It seriously affects patients' quality of life and imposes a significant economic burden on society. Santacruzamate A (SCA) is a natural product isolated from marine cyanobacteria in Panama. In this study, we first demonstrated that SCA could alleviate chronic inflammatory pain, pain-related anxiety, and depression emotions induced by complete Freund's adjuvant in mice while inhibiting microglial activation in the anterior cingulate cortex. Moreover, SCA treatment attenuated lipopolysaccharide (LPS)-induced inflammatory response by downregulating interleukin 1ß and 6 (IL-1ß and IL-6) and tumor necrosis factor-α (TNF-α) levels in BV2 cells. Furthermore, we found that SCA could bind to soluble epoxide hydrolase (sEH) through molecular docking technology, and the thermal stability of sEH was enhanced after binding of SCA to the sEH protein. Meanwhile, we identified that SCA could reduce the sEH enzyme activity and inhibit sEH protein overexpression in the LPS stimulation model. The results indicated that SCA could alleviate the development of inflammation by inhibiting the enzyme activity and expression of sEH to further reduce chronic inflammatory pain. Our study suggested that SCA could be a potential drug for treating chronic inflammatory pain.

Minor Hydroxylated Triterpenoids Produced in Engineered Yeast by the Enzymes OSC and CYP716s from the Plant Enkianthus chinensis and Their Anti-Inflammatory and Hepatoprotective Activities.

Triterpenoids are a type of specialized metabolites that exhibit a wide range of biological activities. However, the availability of some minor triterpenoids in nature is limited, which has hindered our understanding of their pharmacological potential. To overcome this limitation, heterologous biosynthesis of triterpenoids in yeast has emerged as a promising and time-efficient production platform for obtaining these minor compounds. In this study, we analyzed the transcriptomic data of Enkianthus chinensis to identify one oxidosqualene cyclase (EcOSC) gene and four CYP716s. Through heterologous expression of these genes in yeast, nine natural pentacyclic triterpenoids, including three skeleton products (1-3) produced by one multifunctional OSC and six minor oxidation products (4-9) catalyzed by CYP716s, were obtained. Of note, we discovered that CYP716E60 could oxidize ursane-type and oleanane-type triterpenoids to produce 6ß-OH derivatives, marking the first confirmed C-6ß hydroxylation in an ursuane-type triterpenoid. Compound 9 showed moderate inhibitory activity against NO production and dose-dependently reduced IL-1ß and IL-6 production at the transcriptional and protein levels. Compounds 1, 2, 8, and 9 exhibited moderate hepatoprotective activity with the survival rates of HepG2 cells from 61% to 68% at 10 µM.

The heterogeneity of tumour-associated macrophages contributes to the clinical outcomes and indications for immune checkpoint blockade in colorectal cancer patients.

Tumor-associated macrophages (TAMs), one of the major immune cell types in colorectal cancer (CRC) tumor microenvironment (TME), play indispensable roles in immune responses against tumor progression. In this study, we aimed to know whether the extensive inter and intra heterogeneity of TAMs contributes to the clinical outcomes and indications for immune checkpoint blockade (ICB) in CRC. We used single-cell RNA sequencing (scRNA-Seq) data from 60 CRC patients and charactrized TAMs based on anatomic locations, tumor regions, stages, grades, metastatic status, MSS/MSI classification and pseudotemporal differentiation status. We then defined a catalog of 21 gene modules that determine macrophage status, and identified 7 of them as relevant to clinical outcomes and 11 as indications for ICB therapy. On this basis, we constructed a unique TAM subgroup profile, aiming to find features that may be highly responsive to immunotherapy for the CRC with poor prognosis under conventional treatment. This TAM subpopulation is enriched in tumors and is associated with poor prognosis, but exhibits a high immunotherapy response signature (HIM TAM). Further spatial transcriptome analysis and ligand-receptor interaction analysis confirmed that HIM TAM is involved in shaping TIME, especially the regulation of T cells. Our study provides insights into different TAM subtypes, highlights the importance of TAM heterogeneity in relation to patient prognosis and immunotherapy response, and reveals potential immunotherapy strategies based on TAM characteristics for CRC that does not respond well to conventional therapy.

Deciphering the Prognostic Significance of MYD88 and CD79B Mutations in Diffuse Large B-Cell Lymphoma: Insights into Treatment Outcomes.

BACKGROUND: The clinical and genetic characteristics, as well as treatment outcomes, of diffuse large B-cell lymphoma (DLBCL) patients with different MYD88 and CD79B mutation status merit further investigation. OBJECTIVE: This study aims to investigate the distinctions in clinical manifestations, genetic characteristics, and treatment outcomes among MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt DLBCL patients. PATIENTS AND METHODS: Clinical and genetic characteristics, along with treatment outcomes among 2696 DLBCL patients bearing MYD88-CD79Bco-mut, MYD88/CD79Bsingle-mut, and MYD88-CD79Bco-wt treated with R-CHOP/R-CHOP-like regimens from the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and six external cohorts were analyzed. Potential molecular mechanisms were investigated through Gene Set Enrichment Analysis and xCell methodology. RESULTS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable progression-free survival (PFS) and overall survival (OS) compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt. However, in the non-MCD subtype, patients with MYD88-CD79Bco-mut exhibited significantly inferior OS than MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while there was no significant OS difference between MYD88/CD79Bsingle-mut and MYD88-CD79Bco-wt (median OS: 68.8 [95% CI 22-NA] vs NA [95% CI 112-NA] vs 177.7 [95% CI 159-NA] months; MYD88-CD79Bco-mut vs MYD88/CD79Bsingle-mut: p = 0.02; MYD88-CD79Bco-mut vs MYD88-CD79Bco-wt: p = 0.03; MYD88/CD79Bsingle-mut vs MYD88-CD79Bco-wt: p = 0.33). Regarding patients with MYD88-CD79Bco-mut, there was no significant difference in PFS and OS between the MCD and non-MCD subtypes. Within the MYD88-CD79Bco-mut group, patients with PIM1mut had better PFS than PIM1wt (median PFS: 8.34 [95% CI 5.56-NA] vs 43.8 [95% CI 26.4-NA] months; p = 0.02). Possible mechanisms contributing to the superior PFS of PIM1mut patients may include activated lymphocyte-mediated immunity and interferon response, a higher proportion of natural killer T cells and plasmacytoid dendritic cells, as well as suppressed angiogenesis and epithelial-mesenchymal transition, along with lower fibroblast and stromal score. CONCLUSIONS: In the MCD subtype, patients with MYD88-CD79Bco-mut showed comparable PFS and OS compared to MYD88/CD79Bsingle-mut or MYD88-CD79Bco-wt, while in the non-MCD subtype, they exhibited significantly inferior OS. There was no significant disparity in PFS and OS of MYD88-CD79Bco-mut between the MCD and non-MCD subtypes. The presence of PIM1mut within the MYD88-CD79Bco-mut group correlated with better PFS, which may result from an intricate interplay of immune processes and tumor microenvironment alterations.

[Multi-scenario Simulation of Construction Land Expansion and Its Impact on Ecosystem Carbon Storage in Beijing-Tianjin-Hebei Urban Agglomeration].

It is of great practical significance for regional sustainable development and ecological construction to quantitatively analyze the impact of construction land expansion on terrestrial ecosystem carbon storage and to explore the optimization scheme of simulating construction land expansion to improve future ecosystem carbon storage. Based on the land use and cover change (LUCC) and other geospatial data of the Beijing-Tianjin-Hebei Urban Agglomeration from 2000 to 2020, this study utilized the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model and the patch-generating land-use simulation (PLUS) model to assess and analyze the changes in ecosystem carbon stocks and spatial patterns regionally. In this study, we performed linear regression analysis to investigate the relationship between urban land expansion and changes in ecosystem carbon stocks for varying urban land proportion levels during two distinct time intervals, 2000-2010 and 2010-2020, which was conducted at a spatial resolution of 2 km. Three distinct urban land expansion scenarios were subjected to simulation to forecast the prospective land use pattern by 2030. Subsequently, we quantified the ramifications of these scenarios on ecosystem carbon stocks during the period from 2020 to 2030. The results were as follows:① In the Beijing-Tianjin-Hebei Urban Agglomeration, the ecosystem carbon stocks exhibited notable variations over the study period, with values of 2 088.02, 2 106.78, and 2 121.25 Tg recorded for the years 2000, 2010, and 2020, respectively, resulting in a cumulative carbon sequestration of 33.23 Tg C during the study duration. It is noteworthy that forest carbon storage emerged as the dominant contributor, with an increase from 1 010.17 Tg in 2000 to 1 136.53 Tg in 2020. Throughout the study period, the spatial distribution of carbon stocks displayed relative stability. Regions characterized by lower carbon content were concentrated in the vicinity of the Bohai Rim region and in proximity to cities such as Beijing, Tianjin, and Shijiazhuang, as well as rural settlements. In contrast, grid units with moderate and high carbon stocks were predominantly situated in the western Taihang Mountain and the northern Yanshan Mountain. Additionally, there was a tendency of increasing carbon stocks in the Taihang Mountain and Yanshan Mountain region, whereas those surrounding major urban centers such as Beijing, Tianjin, Shijiazhuang, and Tangshan experienced a notable decline in carbon stocks. Such reductions were most pronounced in regions undergoing urban land expansion during the study period. ② In grid units with an urban land proportion exceeding 10% at each level, a strong correlation was observed between urban land expansion and changes in carbon stocks during both the 2000-2010 and 2010-2020 periods. The changes in urban land proportion adequately explained the variations in carbon stocks. However, the explanatory power of urban land on carbon stocks decreased during the 2010-2020 period, indicating that other factors played a more substantial role in influencing carbon stocks during this time. The regression coefficients for both periods exhibited a fluctuating upward trend. In comparison to that during the 2000-2010 period, the impact of urban land expansion on carbon stocks was relatively smaller during 2010-2020, indicating a weakening influence. ③ In light of three distinct development scenarios, namely natural development (Scenario Ⅰ), a 15% reduction in the rate of urban land expansion (Scenario Ⅱ), and a 30% reduction in the rate of urban land expansion (Scenario Ⅲ), the projected ecosystem carbon stocks for the Beijing-Tianjin-Hebei Urban Agglomeration in the year 2030 were estimated to be 2 129.12, 2 133.55, and 2 139.10 Tg, respectively. These projections indicated an increase of 7.88, 12.30, and 17.85 Tg in comparison to the current carbon stocks. All scenarios demonstrated that the terrestrial ecosystem would play a role of carbon sink, particularly with the greatest carbon sink observed in the scenario with a 30% reduction in urban land expansion. The fit performance between urban land expansion and carbon stock changes during the 2020-2030 period was significantly better than that during the 2000-2010 and 2010-2020 periods, and the regression coefficients showed a fluctuating increase with an increase in urban land proportion. Across grid units with different urban land proportion levels, the regression coefficients exhibited the order of Scenario Ⅰ < Scenario Ⅱ < Scenario Ⅲ. In pursuit of the carbon peaking and carbon neutrality goals, the Beijing-Tianjin-Hebei Urban Agglomeration should prioritize scenarios with reduced rates of urban land expansion, especially in regions with higher urban land proportions.

Utilizing Joukowsky transformation in the design of optical fiber for elliptical-to-circular mode conversion.

This study addresses the challenge of enhancing coupling efficiency between optical fibers and elliptical Gaussian beams emitted by semiconductor lasers, particularly in fiber communication systems. We introduce a method for fiber design utilizing the Joukowsky transformation to facilitate efficient mode transformation from elliptical to circular, thereby augmenting the coupling efficiency with both single-mode and multimode fibers. Theoretical analysis and numerical simulations demonstrate that the fiber with a structurally transitional core maintains high-efficiency mode transformation across various lengths, and its structure has been optimized accordingly. Additionally, our investigation reveals the designed fiber's ability to preserve polarization states, which could have significant implications in precision optical applications. The proposed design offers an approach to improving performance in optical communication systems, especially in wavelength-division multiplexing (WDM) transmission systems and fiber lasers.

Error Analysis of Normal Surface Measurements Based on Multiple Laser Displacement Sensors.

The robotic drilling of assembly holes is a crucial process in aerospace manufacturing, in which measuring the normal of the workpiece surface is a key step to guide the robot to the correct pose and guarantee the perpendicularity of the hole axis. Multiple laser displacement sensors can be used to satisfy the portable and in-site measurement requirements, but there is still a lack of accurate analysis and layout design. In this paper, a simplified parametric method is proposed for multi-sensor normal measurement devices with a symmetrical layout, using three parameters: the sensor number, the laser beam slant angle, and the laser spot distribution radius. A normal measurement error distribution simulation method considering the random sensor errors is proposed. The measurement error distribution laws at different sensor numbers, the laser beam slant angle, and the laser spot distribution radius are revealed as a pyramid-like region. The influential factors on normal measurement accuracy, such as sensor accuracy, quantity and installation position, are analyzed by a simulation and verified experimentally on a five-axis precision machine tool. The results show that increasing the laser beam slant angle and laser spot distribution radius significantly reduces the normal measurement errors. With the laser beam slant angle ≥15° and the laser spot distribution radius ≥19 mm, the normal measurement error falls below 0.05°, ensuring normal accuracy in robotic drilling.

Clinicopathological characteristics and gene mutations in 11 patients with lipoprotein glomerulopathy.

OBJECTIVE: Lipoprotein glomerulopathy (LPG) is a rare disorder characterized by the development of glomerular lipoprotein thrombosis. LPG exhibits familial aggregation, with mutations in the apolipoprotein E (APOE) gene identified as the leading cause of this disease. This study aimed to investigate APOE gene mutations and the clinicopathological features in eleven LPG patients. METHODS: Clinicopathological and follow-up data were obtained by extracting DNA, followed by APOE coding region sequencing analysis. This study analyzed clinical and pathological manifestations, gene mutations, treatment and prognosis. RESULTS: The mean age of the eleven patients was 33.82 years. Among them, five had a positive family history for LPG, ten presented with proteinuria, four exhibited nephrotic syndrome, and six presented with microscopic hematuria. Dyslipidemia was identified in ten patients. In all renal specimens, there was evident dilation of glomerular capillary lumens containing lipoprotein thrombi, and positive oil red O staining was observed in frozen sections of all samples. APOE gene testing revealed that one patient had no mutations, while the remaining ten patients exhibited mutations in the APOE gene, with three patients presenting with multiple mutations simultaneously. Following the confirmation of LPG diagnosis, treatment with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) was initiated, and the disease progressed slowly. CONCLUSION: LPG is histologically characterized by lamellated lipoprotein thrombi in glomeruli, and kidney biopsy is essential for diagnosis. Mutations in the APOE gene are the leading cause of LPG. This study revealed clinicopathological characteristics and APOE gene mutations in patients with LPG, which helps us better understand the disease.

Vitamin B5 supplementation enhances intestinal development and alters microbes in weaned piglets.

This study explored the effects of different vitamin B5 (VB5) levels on intestinal growth and function of weaned piglets. Twenty-one piglets (7.20 ± 1.11 kg) were included in a 28-day feeding trial with three treatments, including 0 mg/kg (L-VB5), 10 mg/kg (Control) and 50 mg/kg (H-VB5) of VB5 supplement. The results showed that: Large intestine weight/body weight was the highest in H-VB5 group, Control and H-VB5 groups had significantly higher villus height and villus height/crypt depth than the L-VB5 in the ileum (p < .05). Goblet cells (ileal crypt) and endocrine cells (ileal villus) significantly increased in Control and H-VB5 (p < .05). The H-VB5 group exhibited significantly higher levels of ki67 and crypt depth in the cecum and colon, colonic goblet cells and endocrine cells were both rising considerably (p < .05). Isobutyric acid and isovaleric acid were significantly reduced in the H-VB5 group (p < .05), and there was a decreasing trend in butyric acid (p = .073). At the genus level, the relative abundance of harmful bacteria such as Clostridium_Sensu_Structo_1 Strecto_1, Terrisporbacter and Streptococcus decreased significantly and the relative abundance of beneficial bacteria Turicibacter increased significantly in H-VB5 group (p < .05). Overall, the addition of 50 mg/kg VB5 primarily enhanced the morphological structure, cell proliferation and differentiation of the ileum, cecum and colon. It also had a significant impact on the gut microbiota and short-chain fatty acids.

Exosome secretion related gene signature predicts chemoresistance in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly heterogeneous malignancy, and patients often have different responses to treatment. In this study, the genetic characteristics related to exosome formation and secretion procedure were used to predict chemoresistance and guide the individualized treatment of patients. METHODS: Firstly, seven microarray datasets in Gene Expression Omnibus (GEO) and RNA-Seq dataset from the Cancer Genome Atlas (TCGA) were used to analysis the transcriptome profiles and associated characteristics of CRC patients. Then, a predictive model based on gene features linked to exosome formation and secretion was created and validated using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning. Finally, we evaluated the model using chemoresistant/chemosensitive cells and tissues by immunofluorescence (IF), western blot (WB), quantitative real-time PCR (qRT-PCR) and immunocytochemistry (IHC) experiments, and the predictive value of integrated model in the clinical validation cohort were performed by Receiver Operating Characteristic (ROC) and Kaplan-Meier (K-M) curves analyses. RESULTS: We established a risk score signature based on three genes related to exosome secretion in CRC. Better Overall Survival (OS) and greater chemosensitivity were seen in the low-risk group, whereas the high-risk group exhibited chemoresistance and a subpar response to immune checkpoint blockade (ICB) therapy. Higher expression of the model genes EXOC2, EXOC3 and STX4 were observed in chemoresistant cells and specimens. The AUC of 5-year disease-free survival (DFS) was 0.804. Compared with that in the low-risk group, patients' DFS was found to be significantly worse in the high-risk group. CONCLUSIONS: In summary, the gene signature related to exosome formation and secretion could reliably predict patients' chemosensitivity and ICB treatment response, which providing new independent biomarkers for the treatment of CRC.