Deciphering the impact of aggregated autophagy-related genes TUBA1B and HSP90AA1 on colorectal cancer evolution: a single-cell sequencing study of the tumor microenvironment.

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with the tumor microenvironment (TME) playing a crucial role in its progression. Aggregated autophagy (AA) has been recognized as a factor that exacerbates CRC progression. This study aims to study the relationship between aggregated autophagy and CRC using single-cell sequencing techniques. Our goal is to explain the heterogeneity of the TME and to explore the potential for targeted personalized therapies. OBJECTIVE: To study the role of AA in CRC, we employed single-cell sequencing to discern distinct subpopulations within the TME. These subpopulations were characterized by their autophagy levels and further analyzed to identify specific biological processes and marker genes. RESULTS: Our study revealed significant correlations between immune factors and both clinical and biological characteristics of the tumor microenvironment (TME), particularly in cells expressing TUBA1B and HSP90AA1. These immune factors were associated with T cell depletion, a reduction in protective factors, diminished efficacy of immune checkpoint blockade (ICB), and enhanced migration of cancer-associated fibroblasts (CAFs), resulting in pronounced inflammation. In vitro experiments showd that silencing TUBA1B and HSP90AA1 using siRNA (Si-TUBA1B and Si-HSP90AA1) significantly reduced the expression of IL-6, IL-7, CXCL1, and CXCL2 and inhibition of tumor cell growth in Caco-2 and Colo-205 cell lines. This reduction led to a substantial alleviation of chronic inflammation and highlighted the heterogeneous nature of the TME. CONCLUSION: This study marks an initial foray into understanding how AA-associated processes may potentiate the TME and weaken immune function. Our findings provide insights into the complex dynamics of the TME and highlight potential targets for therapeutic intervention, suggesting a key role for AA in the advancement of colorectal cancer.

Polymorphism of Niobium Phosphate Bronze Na4Nb8P4O32 Deduced by the Packings of Structural Units: A Centrosymmetric Phase.

Herein, a new centrosymmetric phase Na4Nb8P4O32 (referred to as CS-Na4Nb8P4O32) was obtained by a molten salt method, which is a polymorph of niobium phosphate bronze Na4Nb8P4O32. CS-Na4Nb8P4O32 displays high structural similarity to the noncentrosymmetric Na4Nb8P4O32 phase (referred to as NCS-Na4Nb8P4O32): Distorted NbO6 octahedra are corner-coordinated to form ReO3-type layers, which are further joined together by isolated PO4 tetrahedra. However, two polymorphous phases adopt different packings of structural units, resulting in distinct symmetries. NbO3 layers and PO4 tetrahedra are reversely arranged along the crystallographic a direction in CS-Na4Nb8P4O32, thereby producing a centrosymmetric structure. The reverse packing cancels out all contributions of dipole moments originating from the distorted NbO6 octahedra; NCS-Na4Nb8P4O32 exhibits the C2-rotation distribution of NbO3 layers and PO4 tetrahedra, thus generating a noncentrosymmetric and polar structure. The C2-rotation packing of structural units brings a constructive addition of the dipole moments, further obtaining large calculated independent second harmonic generation susceptibilities. The study of structural evolution deduced by the packings of structural units in polymorphous Na4Nb8P4O32 might provide valuable insights into polymorphism and structural regulation.

Co-substitution design: a new glaserite-type rare-earth phosphate K2RbSc(PO4)2 with high structural tolerance.

An alkali rare-earth phosphate K2RbSc(PO4)2 was successfully obtained as a derivative of glaserite-type K3Na(SO4)2 by co-substitution of K(1)O12 → RbO12, K(2)O10 → KO7, NaO6 → ScO6 and SO4 → PO4, while maintaining the original anionic framework. K2RbSc(PO4)2 exhibits a layered [Sc(PO4)2]∞ framework built from ScO6 octahedra and PO4 tetrahedra, with K and Rb residing in the interlayers. Its isostructural lanthanide analogues K2RbEr(PO4)2 and K2RbLu(PO4)2, inspired by an elemental substitution strategy, were also prepared by a high-temperature solid state reaction. The successful substitution indicates that the skeleton of K2RbSc(PO4)2 is stable with high structural tolerance, which can provide a possibility for substitution of resident ions to obtain diverse structural types and applications.

Anti-reflux effects of a novel esophagogastric asymmetric anastomosis technique after laparoscopic proximal gastrectomy.

BACKGROUND: Reflux esophagitis is a common postoperative complication of proximal gastrectomy. There is an urgent need for a safer method of performing esophageal-gastric anastomosis that reduces the risk of reflux after proximal gastrectomy. We hypothesize that a novel technique termed esophagogastric asymmetric anastomosis (EGAA) can prevent postoperative reflux in a safe and feasible manner. AIM: To observe a novel method of EGAA to prevent postoperative reflux. METHODS: Initially, we employed a thermal stress computer to simulate and analyze gastric peristalsis at the site of an esophagogastric asymmetric anastomosis. This was done in order to better understand the anti-reflux function and mechanism. Next, we performed digestive tract reconstruction using the EGAA technique in 13 patients who had undergone laparoscopic proximal gastrectomy. Post-surgery, we monitored the structure and function of the reconstruction through imaging exams and gastroscopy. Finally, the patients were followed up to assess the efficacy of the anti-reflux effects. RESULTS: Our simulation experiments have demonstrated that the clockwise contraction caused by gastric peristalsis and the expansion of the gastric fundus caused by the increase of intragastric pressure could significantly tighten the anastomotic stoma, providing a means to prevent the reverse flow of gastric fluids. Thirteen patients with esophagogastric junction tumors underwent laparoscopic proximal gastrectomy, with a mean operation time of 304.2 ± 44.3 min. After the operation, the upper gastroenterography in supine/low head positions showed that eight patients exhibited no gastroesophageal reflux, three had mild reflux, and two had obvious reflux. The abdominal computed tomography examination showed a valve-like structure at the anastomosis. During follow-up, gastroscopy revealed a closed valve-like form at the anastomosis site without stenosis or signs of reflux esophagitis in 11 patients. Only two patients showed gastroesophageal reflux symptoms and mild reflux esophagitis and were treated with proton pump inhibitor therapy. CONCLUSION: EGAA is a feasible and safe surgical method, with an excellent anti-reflux effect after proximal gastrectomy.

Gut microbiota alterations in children and their relationship with primary immune thrombocytopenia.

Introduction: Gut microbiota reportedly play a critical role in some autoimmune diseases by maintaining immune homeostasis. Only a few studies have examined the correlation between gut microbiota and the onset of primary immune thrombocytopenia (ITP), especially in children. The purpose of this study was to investigate changes in the composition and diversity of the fecal microbiota of children with ITP, as well as the correlation between such microbiota and the onset of ITP. Methods: Twenty-five children newly diagnosed with ITP and 16 healthy volunteers (controls) were selected for the study. Fresh stool samples were collected to identify changes in the composition and diversity of gut microbiota as well as for potential correlation analysis. Results: In ITP patients, the phyla that were most frequently encountered were Firmicutes (54.3%), followed by Actinobacteria (19.79%), Bacteriodetes (16.06%), and Proteobacteria (8.75%). The phyla that were predominantly found in the controls were, Firmicutes (45.84%), Actinobacteria (40.15%), Bacteriodetes (3.42%), and Proteobacteria (10.23%). Compared with those of the controls, the proportions of Firmicutes and Bacteriodetes in the gut microbiota of ITP patients were increased while the proportions of Actinobacteria and Proteobacteria were decreased. Furthermore, gut microbiota in ITP patients varied by age group, showed specific changes in diversity, and were correlated with antiplatelet antibodies. IgG levels were significantly positively correlated with Bacteroides (P<0.01). Conclusions: The gut microbiota of children with ITP are imbalanced, as shown by the increase in Bacteroidetes, which was positively correlated with IgG. Thus gut microbiota may contribute to ITP pathogenesis via IgG. Clinical Trial Registration: The clinical trial were registered and approved by the Institutional Review Committee of The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University. Ethics number KY-2023-106-01.

Atomic Substitution to Tune ScO6 Distortion in Ba2MSc2(BO3)4 (M = Na, K, Ba) to Acquire a Large Birefringence.

Replacing alkali metals (K, Na atoms) by an alkaline-earth metal (Ba atom), α-Ba3Sc2(BO3)4 (high-temperature phase) is successfully obtained by a molten salt method, taking Ba2K1.6Na0.4Sc2(BO3)4 as the parent template. Although both of them exhibit similar layered structures composed of ScO6 and BO3 units, α-Ba3Sc2(BO3)4 shows largely distorted ScO6 octahedra (Δd = 0.56) forced by the uniform tension of a larger space effect from BaO12 polyhedrons, rather than regular ScO6 octahedra like in Ba2K1.6Na0.4Sc2(BO3)4. Experimental measurements and calculated analyses elucidate that distorted ScO6 octahedra in α-Ba3Sc2(BO3)4, displaying a second-order Jahn-Teller (SOJT) effect, enlarge the experimental birefringence up to 0.14@550 nm, while Ba2K1.6Na0.4Sc2(BO3)4 with regular ScO6 octahedra only shows Δn = 0.11 under the same condition. In addition, other optical and thermal properties of the two title compounds were characterized. The experimental results indicate that Ba2K1.6Na0.4Sc2(BO3)4 and α-Ba3Sc2(BO3)4 are promising birefringent materials.

Proton-Rich POM-Type K12Mo8O20(HPO4)8(PO4)Cl with Ion-Exchange Capabilities.

A proton-rich POM-type molybdenum phosphate K12Mo8O20(HPO4)8(PO4)Cl was successfully obtained. It crystallizes in a noncentrosymmetric tetragonal space group of P-4 (No. 81) with the unit cell parameters of a = 9.6580(4) Å, c = 14.2607(10) Å, and Z = 1. The occurrence and positions of the light element H in the structure are inferred from single-crystal X-ray diffraction and confirmed by DFT calculations. The hydrogen atoms are found to form hydroxyl bonds with O atoms from P(2)O4 and P(3)O4 constituting the [Mo4P4O26H4]4- layers but are only weakly bound to the isolated P(3)O4 group through hydrogen bonds. The title compound presents a POM-type framework of corrugated [Mo4P4O26H4]4- layers with four K+ ions and mixed ions (K4Cl3+ and isolated PO43-) orderly imbedding in the interlayer spaces with distances of 5.0396 (1) and 5.5966 (3) Å, respectively. The proton-rich nature and the structure feature were further verified by a series of experiments including 1H, 7Li, and 31P MAS NMR spectra, IR spectroscopy, and thermal analysis. Moreover, the weak bonding and large interlayer spaces make K+ and H+ ions susceptible to exchange with ions of Cs+, Ba2+, Zn2+, Pb2+, Cu2+, and Ni2+ commonly presented in chemical pollutants or nuclear wastes. In addition, the title compound shows a small second-harmonic generation signal, consistent with its noncentrosymmetric structure.

Introducing a New d0 Sc3+ Asymmetric Ion for Functional Materials: Large Birefringence Enhancement by ScO6 in Ba3 Sc2 (BO3 )4.

Transition metal ions with d0 electronic states (Ti4+ , Zr4+ , Nb5+ and Ta5+ ) are widely investigated as functional materials. This work first illustrates that Sc3+ ion, long-time ignored, displays a second-order Jahn-Teller (SOJT) effect similar to asymmetric oxide-coordinated transition metal ions, thus providing a new ground to seek for asymmetric functional materials with enhanced performances. In Ba3 Sc2 (BO3 )4 , BO3 groups are parallelly arranged, satisfying the ideal arrangement to produce large birefringence. Importantly, distorted octahedral ScO6 with Sc3+ ion in its d0 electronic state enlarges birefringence unexpectedly up to 0.149 @ 550 nm, which is larger than previously reported borates containing solely BO3 , even to B3 O6 units. Subsequently, the SOJT influence of distorted ScO6 octahedra on birefringence is verified by a comparison between experimental data and theoretical calculations. In addition, Ba3 Sc2 (BO3 )4 also displays a high transmittance in the range of 230 nm-3.5 µm with a UV cut-off wavelength at 198 nm and a large laser induced damage threshold (2.7 GW/cm2 ), comparable to α-BaB2 O4 . Above characteristics imply that the title compound may be a promising birefringent material.

Ca3(TeO3)2(MO4) (M = Mo, W): Mid-Infrared Nonlinear Optical Tellurates with Ultrawide Transparency Ranges and Superhigh Laser-Induced Damage Thresholds.

Intense interests in mid-infrared (MIR) nonlinear optical (NLO) crystals have erupted in recent years due to the development of optoelectronic applications ranging from remote monitoring to molecular spectroscopy. Here, two polar crystals Ca3(TeO3)2(MO4) (M = Mo, W) were grown from TeO2-MO3 flux by high-temperature solution methods. Ca3(TeO3)2(MoO4) and Ca3(TeO3)2(WO4) are isostructural, which feature novel structures consisting of asymmetric MO4 tetrahedra and TeO3 trigonal pyramids. Optical characterizations show that both crystals display ultrawide transparency ranges (279 nm to 5.78 µm and 290 nm to 5.62 µm), especially high optical transmittance over 80% in the important atmospheric transparent window of 3-5 µm, and superhigh laser damage thresholds (1.63 GW/cm2 and 1.50 GW/cm2), 54.3 and 50 times larger than that of state-of-the-art MIR NLO AgGaS2, respectively. Notably, they exhibit the widest band gaps and the loftiest laser-induced threshold damages among the reported tellurates so far. Moreover, Ca3(TeO3)2(MO4) exhibit type I phase matching at two working wavelengths owing to their large birefringence and strong second-harmonic generation responses from the distorted anions, as further elucidated by the first-principles calculations. The above characteristics indicate that Ca3(TeO3)2(MO4) crystals are high-performance MIR NLO materials, especially applying in high-power MIR laser operations.

A Titanium and Tantalum Phosphate LiNaTiTa2 P2 O13 with An Open Framework hosting Li and Na Ions.

Herein, we report a detailed structural, electric, thermal and optical analysis of a titanium and tantalum phosphate LiNaTiTa2 P2 O13 . The title compound is comprised of typical ReO3 -type layers constituted by corner-sharing TiO6 and TaO6 octahedra, bridged by PO4 tetrahedra, and the structure is closely related to monophosphate niobium bronzes. The existence of pentagonal tunnels, hosting the Li+ and Na+ ions, endows LiNaTiTa2 P2 O13 a moderate ion transportation behavior (4.67×10-4  S/cm at 823 K). In addition, the successful substitution of Nb for Ta in LiNaTiTa2 P2 O13 results in the optical absorption red-shift towards visible range with a narrowing band gap, which may provide a route of isomorphic replacement to band engineering for photo-catalysis.

Incidence of and risk factors for surgical site infection after colorectal surgery: A multiple-center prospective study of 3,663 consecutive patients in China.

BACKGROUND: Surgical site infection (SSI) after colorectal surgery (CRS) remains a significant problem for its negative clinical outcomes. However, it is poorly understood in China. This study aims to investigate the incidence, risk factors and microbiology of SSI after CRS. METHODS: A nationwide prospective multicenter design was applied. Patients in 19 Chinese hospitals from 2015 to 2018 were prospectively monitored for SSI after CRS. Demographic data, hospital characteristics, and potential perioperative risk factors were collected and analyzed, using univariate and multivariate logistic regression models. RESULTS: Among 3,663 study participants, 134(3.66%) episodes of SSI were identified. The incidence rate of SSI decreased from 5.9 infections per 100 procedures in 2015 to 3.1 infections per 100 procedures in 2018 (incidence rate ratio, 0.52; 95% CI, 0.28-0.94). The SSI rates were 1.88, 4.15, 6.27 and 11.58 per 100 operations for the National Nosocomial Infections Surveillance system (NNIS) risk index categories of 0, 1, and 2 or 3, respectively. Escherichia coli (54/134, 40.3%) and Klebsiella pneumoniae (10/134, 7.5%) were the most frequently isolated microorganisms. A high prevalence of antibiotic resistance were observed in our study, with rates of extended spectrum beta-lactamase-producing or carbapenem-resistant Escherichia coli and Klebsiella pneumonia of 50.0%(27/54) and 30.0%(3/10) respectively. Preoperative hospital stay ≥ 48h (OR=2.28, 95% CI: 1.03-5.02, P=0.042) and contaminated or dirty wound (OR=3.38, 95% CI: 1.88-6.06, P=4.50×10-5) were significantly associated with increasing risk of SSI after CRS. CONCLUSION: A statistically significant but modest decrease in the incidence rate of CRS SSI over the 4-year study period was observed in this study. Noticeably, the relatively high rates of multidrug-resistant pathogens causing SSI after CRS should be alert, while more studies with large population are needed due to the small number of isolates identified in our survey.

Efficacy of Serum Total Bilirubin in Predicting the Severity of Ulcerative Colitis: A Cross-Sectional Study.

OBJECTIVE: Several serum parameters can be used to assess ulcerative colitis (UC) disease activity. However, the value of these parameters for predicting UC severity has not been studied in depth. Therefore, we sought to investigate the value of serum total bilirubin (TB) as a predictor of UC severity. MATERIALS AND METHODS: This cross-sectional study included 448 UC patients and 308 healthy participants. Data regarding the serum levels of TB, hemoglobin (Hb), albumin (Alb), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were collected. UC severity was evaluated according to the Truelove and Witts criteria. Wilcoxon rank sum tests were used to compare data between groups, while Spearman correlation analyses between TB and the levels of Hb, Alb, ESR and CRP were performed. Logistic regression analyses were used to determine the odds ratios (ORs) for severe UC in UC patients. RESULTS: UC patients had lower Hb, Alb, and TB levels than healthy participants (p<0.001). The Hb, Alb, and TB levels were lower in severe UC patients than in mild-to-moderate UC patients (p<0.001). TB was positively correlated with Hb and Alb, but negatively correlated with ESR and CRP (p<0.05). Logistic regression analysis revealed that the ORs for severe UC were 2.35 and 2.04 at TB concentrations of ≤8.00 µmol/L and 8.01-10.90 µmol/L, respectively (p<0.05). CONCLUSIONS: Serum TB level is an effective predictor of the severity of UC.

Prevalence of healthcare-associated infections and antimicrobial use in China: Results from the 2018 point prevalence survey in 189 hospitals in Guangdong Province.

BACKGROUND: Limited data on healthcare-associated infections (HAIs) are available from the developing world, thus a point prevalence survey was conducted to determine the prevalence of HAIs and antimicrobial use in Guangdong Province, China. METHODS: A standardized methodology for point prevalence surveys on HAIs and antimicrobial use has been developed by the Chinese Nosocomial Infection Control and Quality Improvement Center. The prevalence of HAIs, antimicrobial use, and baseline hospital-level variables were collected in 189 hospitals from June 2017 to May 2018. RESULTS: Of 5 868 147 patients, 72 976 had one or more HAIs (1.24%), with 82 700 distinct HAIs. The prevalence rates of device-associated infections, including ventilator-associated pneumonia, catheter-associated urinary tract infection, and central line-associated bloodstream infection were 7.92, 2.06, and 0.63 per 1000 catheter-days, respectively. A total of 10 591 (0.18%) HAIs caused by multidrug-resistant organisms were identified. Carbapenem non-susceptibility rates were highest in Acinetobacter species (53.86%) and Pseudomonas aeruginosa (21.60%). Forty-six percent (2 712 258/5 868 147) of inpatients were receiving at least one antimicrobial during this survey. CONCLUSIONS: This survey indicated the relatively lower prevalence of HAIs but higher antimicrobial using in Guangdong Province compared with other mid to low-income and high-income countries. Further studies are warranted to elucidate which HAI-related indicators are the best measures of HAI performance and thus allow improvements leading to better patient outcomes.

Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report.

INTRODUCTION: Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for ulcerative colitis (UC). Here, we report the first case of a UC patient with allergy to 5-aminosalicylic acid (5-ASA) who underwent FMT and achieved clinical remission. CASE PRESENTATION: This patient had a 9-year history of UC and was allergic to 5-ASA. He suffered from gradually aggravated abdominal pain and frequent bloody diarrhea. There was a continuous distribution of superficial erosion and ulceration by colonoscopy. After steroid therapy failed, he underwent FMT. The donated fecal microbes were purified in laboratory and then transplanted into the terminal ileum and right colon of the patient by colonoscopy. During the 9 months' follow-up, FMT has proved its efficacy in inducing and maintaining clinical and endoscopic remission of the patient. CONCLUSION: The choice of treatment for refractory UC patients who are allergic to 5-ASA is relatively limited. In our case, we highlight the specific role of FMT for refractory UC with absence of 5-ASA through intestinal microbiota reconstruction.

MicroRNA-615-5p targets insulin-like growth factor 2 and exerts tumor-suppressing functions in human esophageal squamous cell carcinoma.

To investigate the expression pattern, clinical significance and functional roles of microRNA (miR)-615-5p in human esophageal squamous cell carcinoma (ESCC), , quantitative real-time PCR was performed to detect expression levels of miR­615­5p in ESCC tissues and cell lines. Associations between miR­615­5p expression and various clinicopathological features of ESCC patients were also statistically evaluated. The candidate targets of miR­615­5p were identified by integrating bioinformatics miRNA target prediction, western blot analysis and luciferase reporter assay. Moreover, the functions of miR­615­5p in ESCC cell migration and invasion were determined using the transfection of miRNA mimics, or co-transfected with miRNA mimics and the expression vector of its target gene. As a result, miR­615­5p expression in ESCC tissues and cells were markedly lower than those in non-cancerous esophageal mucosa and human normal esophageal cells, respectively (both P<0.001). miR­615­5p downregulation was significantly associated with advanced tumor-node-metastasis stage, positive lymph node metastasis and moderate-poor differentiation. Functionally, the re-expression of miR­615­5p suppressed the invasion and migration of ESCC cells in vitro. Interestingly, insulin-like growth factor 2 (IGF2) was identified as a direct target gene of miR­615­5p, and the inhibitory effects of miR­615­5p in ESCC cell motility were reversed by the restoration of IGF2 expression. In conclusion, miR­615­5p downregulation may be an underlying molecular mechanism of development and progression of ESCC, and may function as a potential therapeutic target of this malignancy. Also, we illustrate that the miR­615­5p/IGF2 axis may bring important contributions to cell motility of human ESCC.

Defect-rich MoS2 ultrathin nanosheets with additional active edge sites for enhanced electrocatalytic hydrogen evolution.

Defect-rich MoS2 ultrathin nanosheets are synthesized on a gram scale for electrocatalytic hydrogen evolution. The novel defect-rich structure introduces additional active edge sites into the MoS2 ultrathin nanosheets, which significantly improves their electrocatalytic performance. Low onset overpotential and small Tafel slope, along with large cathodic current density and excellent durability, are all achieved for the novel hydrogen-evolution-reaction electrocatalyst.

Atomically thin tin dioxide sheets for efficient catalytic oxidation of carbon monoxide.

The thinner the better: SnO2 sheets that are five atomic layers thick are an efficient catalyst for the oxidation of CO. These sheets, which have 40% surface atom occupancy and are fabricated by a scalable ethylenediamine-assisted pathway, show remarkably improved catalytic performances compared to other SnO2 species, with the apparent activation energy lowered to 59.2 kJ mol(-1) and the full-conversion-temperature lowered to 250 °C.

Nanopatterning on silicon surface using atomic force microscopy with diamond-like carbon (DLC)-coated Si probe.

Atomic force microscope (AFM) equipped with diamond-like carbon (DLC)-coated Si probe has been used for scratch nanolithography on Si surfaces. The effect of scratch direction, applied tip force, scratch speed, and number of scratches on the size of the scratched geometry has been investigated. The size of the groove differs with scratch direction, which increases with the applied tip force and number of scratches but decreases slightly with scratch speed. Complex nanostructures of arrays of parallel lines and square arrays are further fabricated uniformly and precisely on Si substrates at relatively high scratch speed. DLC-coated Si probe has the potential to be an alternative in AFM-based scratch nanofabrication on hard surfaces.

Preface to special topic: surface modification, wetting, and biological interfaces (guest editors: john ralston and jingfang zhou).

This Special Topic section of Biomicrofluidics on "Surface Modification, Wetting, and Biological Interfaces," is discussed. The topic is very timely and one that is tremendously relevant to the microfluidics and nanofluidics community.