Mild-Temperature Supercritical Water Confined in Hydrophobic Metal-Organic Frameworks.

Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, ∼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.

AppleQSM: Geometry-Based 3D Characterization of Apple Tree Architecture in Orchards.

The architecture of apple trees plays a pivotal role in shaping their growth and fruit-bearing potential, forming the foundation for precision apple management. Traditionally, 2D imaging technologies were employed to delineate the architectural traits of apple trees, but their accuracy was hampered by occlusion and perspective ambiguities. This study aimed to surmount these constraints by devising a 3D geometry-based processing pipeline for apple tree structure segmentation and architectural trait characterization, utilizing point clouds collected by a terrestrial laser scanner (TLS). The pipeline consisted of four modules: (a) data preprocessing module, (b) tree instance segmentation module, (c) tree structure segmentation module, and (d) architectural trait extraction module. The developed pipeline was used to analyze 84 trees of two representative apple cultivars, characterizing architectural traits such as tree height, trunk diameter, branch count, branch diameter, and branch angle. Experimental results indicated that the established pipeline attained an R2 of 0.92 and 0.83, and a mean absolute error (MAE) of 6.1 cm and 4.71 mm for tree height and trunk diameter at the tree level, respectively. Additionally, at the branch level, it achieved an R2 of 0.77 and 0.69, and a MAE of 6.86 mm and 7.48° for branch diameter and angle, respectively. The accurate measurement of these architectural traits can enable precision management in high-density apple orchards and bolster phenotyping endeavors in breeding programs. Moreover, bottlenecks of 3D tree characterization in general were comprehensively analyzed to reveal future development.

Oxidation of chromium(â ¢): A potential risk of using chemical oxidation processes for the remediation of 2-chlorophenol contaminated soils.

Chemical oxidation processes are widely used for the remediation of organically contaminated soils, but their potential impact on variable-valence and toxic metals such as chromium (Cr) is often overlooked. In this study, we investigated the risk of Cr(Ⅲ) oxidation in soils during the remediation of 2-chlorophenol (2-CP) contaminated soils using four different processes: Potassium permanganate (KMnO4), Modified Fenton (Fe2+/H2O2), Alkali-activated persulfate (S2O82-/OH-), and Fe2+-activated persulfate (S2O82-/Fe2+). Our results indicated that the KMnO4, Fe2+/H2O2, and S2O82-/Fe2+ processes progressively oxidized Cr(III) to Cr(Ⅵ) during the 2-CP degradation. The KMnO4 process likely involved direct electron transfer, while the Fe2+/H2O2 and S2O82-/Fe2+ processes primarily relied on HO• and/or SO4•- for the Cr(III) oxidation. Notably, after 4 h of 2-CP degradation, the Cr(VI) content in the KMnO4 process surpassed China's 3.0 mg kg-1 risk screening threshold for Class I construction sites, and further exceeded the 5.7 mg kg-1 limit for Class II construction sites after 8 h. Conversely, the S2O82-/OH- process exhibited negligible oxidation of Cr(III), maintaining a low oxidation ratio of 0.13%, as highly alkaline conditions induced Cr(III) precipitation, reducing its exposure to free radicals. Cr(III) oxidation ratio was directly proportional to oxidant dosage, whereas the Fe2+/H2O2 process showed a different trend, influenced by the concentration of reductants. This study provides insights into the selection and optimization of chemical oxidation processes for soil remediation, emphasizing the imperative for thorough risk evaluation of Cr(III) oxidation before their application.

Chromosomal 3q amplicon encodes essential regulators of secretory vesicles that drive secretory addiction in cancer.

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role as a scaffold, GOLIM4 maintains intracellular manganese (Mn) homeostasis by binding excess Mn in the Golgi lumen, which initiates the routing of Mn-bound GOLIM4 to lysosomes for degradation. We show that Mn treatment inhibits the progression of multiple types of 3q-amplified malignancies by degrading GOLIM4, resulting in a secretory blockade that interrupts pro-survival autocrine loops and attenuates pro-metastatic processes in the tumor microenvironment. Potentially underlying the selective activity of Mn against 3q-amplified malignancies, ATP2C1 co-amplification increases Mn influx into the Golgi lumen, resulting in a more rapid degradation of GOLIM4. These findings show that functional cooperativity between co-amplified genes underlies heightened secretion and a targetable secretory addiction in 3q-amplified malignancies.

Novel CDK19-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake.

Cyclin-dependent kinase 19 (CDK19) is overexpressed in prostate cancer, making it an attractive target for both imaging and therapy. Since little is known about the optimized approach for radioligands of nuclear proteins, linker optimization strategies were used to improve pharmacokinetics and tumor absorption, including the adjustment of the length, flexibility/rigidity, and hydrophilicity/lipophilicity of linkers. Molecular docking was conducted for virtual screening and followed by IC50 determination. Both BALB/c mice and P-16 xenografts were used for tissue distribution and PET/CT imaging. The ligand 68Ga-10c demonstrated high absorption in tumor 5 min after injection and sustains long-term imaging within 3 h. Furthermore, 68Ga-10c exhibited slow clearance within the tumor and was predominantly metabolized in both the liver and kidneys, showing the potential to alleviate metabolic pressure and enhance tissue safety. Therefore, the linker optimization strategy is well suited for CDK19 and provides a reference for the radioactive ligands of other nuclear targets.

Exopolysaccharides and Surface-Layer Proteins Expressed by Biofilm-State Lactiplantibacillus plantarum Y42 Play Crucial Role in Preventing Intestinal Barrier and Immunity Dysfunction of Balb/C Mice Infected by Listeria monocytogenes ATCC 19115.

Our previous study showed that Lactiplantibacillus plantarum Y42 in the biofilm state can produce more exopolysaccharides and surface-layer proteins and showed a stronger promoting effect on intestinal barrier function than that in the planktonic state. In this study, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites (exopolysaccharides and surface-layer proteins) increased the expression of Occludin, Claudin-1, ZO-1, and MUC2 in the gut of the Balb/C mice after exposure to Listeria monocytogenes ATCC 19115 and inhibited the activation of the NLRP3 inflammasome pathway, which in turn reduced the levels of inflammatory cytokines IL-1ß and IL-18 in the serum of the mice. Furthermore, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites increased the abundance of beneficial bacteria (e.g., Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001) while reducing the abundance of harmful bacteria (e.g., norank_f__Muribaculaceae) in the gut of the mice, in line with the increase of short-chain fatty acids and indole derivatives in the feces of the mice. Notably, biofilm L. plantarum Y42 exerted a better preventing effect on the intestinal barrier dysfunction of the Balb/C mice due to the fact that biofilm L. plantarumY42 expressed more exopolysaccharides and surface-layer proteins than the planktonic state. These results provide data support for the use of exopolysaccharides and surface-layer proteins extracted from biofilm-state L. plantarum Y42 as functional food ingredients in preventing intestinal barrier dysfunction.

POLQ inhibition attenuates the stemness and ferroptosis resistance in gastric cancer cells via downregulation of dihydroorotate dehydrogenase.

Gastric cancer (GC) contains subpopulations of cancer stem cells (CSCs), which are described as the main contributors in tumor initiation and metastasis. It is necessary to clarify the molecular mechanism underlying CSCs phenotype and develop novel biomarkers and therapeutic targets for gastric cancer. Here, we show that POLQ positively regulates stem cell-like characteristics of gastric cancer cells, knockdown of POLQ suppressed the stemness of GC cells in vitro and in vivo. Further mechanistic studies revealed that POLQ knockdown could downregulate the expression of dihydroorotate dehydrogenase (DHODH). DHODH overexpression rescued the reduced stemness resulted by POLQ knockdown. Furthermore, we found that POLQ expression correlated with resistance to ferroptosis, and POLQ inhibition renders gastric cancer cells more vulnerable to ferroptosis. Further investigation revealed that POLQ regulated DHODH expression via the transcription factors E2F4, thereby regulating ferroptosis resistance and stemness of gastric cancer cells. Given the importance of POLQ in stemness and ferroptosis resistance of GC, we further evaluated the therapeutic potential of POLQ inhibitor novobiocin, the results show that novobiocin attenuates the stemness of GC cells and increased ferroptosis sensitivity. Moreover, the combination of POLQ inhibitor and ferroptosis inducer synergistically suppressed MGC-803 xenograft tumor growth and diminished metastasis. Our results identify a POLQ-mediated stemness and ferroptosis defense mechanism and provide a new therapeutic strategy for gastric cancer.

Establishment and verification of a nomogram that predicts the risk for coronary slow flow.

Background: Coronary slow flow (CSF) has gained significance as a chronic coronary artery disease, but few studies have integrated both biological and anatomical factors for CSF assessment. This study aimed to develop and validate a simple-to-use nomogram for predicting CSF risk by combining biological and anatomical factors. Methods: In this retrospective case-control study, 1042 patients (614 CSF cases and 428 controls) were randomly assigned to the development and validation cohorts at a 7:3 ratio. Potential predictive factors were identified using least absolute shrinkage and selection operator regression and subsequently utilized in multivariate logistic regression to construct the nomogram. Validation of the nomogram was assessed by discrimination and calibration. Results: N-terminal pro brain natriuretic peptide, high density lipoprotein cholesterol, hemoglobin, left anterior descending artery diameter, left circumflex artery diameter, and right coronary artery diameter were independent predictors of CSF. The model displayed high discrimination in the development and validation cohorts (C-index 0.771, 95% CI: 0.737-0.805 and 0.805, 95% CI: 0.757-0.853, respectively). The calibration curves for both cohorts showed close alignment between predicted and actual risk estimates, demonstrating improved model calibration. Decision curve analysis suggested high clinical utility for the predictive nomogram. Conclusion: The constructed nomogram accurately and individually predicts the risk of CSF for patients with suspected CSF and may be considered for use in clinical care.

A novel intelligent model for visualized inference of medical diagnosis: A case of TCM.

How to present an intelligent model based on known diagnostic knowledge to assist medical diagnosis and display the reasoning process is an interesting issue worth exploring. This study developed a novel intelligent model for visualized inference of medical diagnosis with a case of Traditional Chinese Medicine (TCM). Four classes of TCM's diagnosis composed of Yin deficiency, Liver Yin deficiency, Kidney Yin deficiency, and Liver-Kidney Yin deficiency were selected as research examples. According to the knowledge of diagnostic points in "Diagnostics of TCM", a total of 2000 samples for training and testing were randomly generated for the four classes of TCM's diagnosis. In addition, a total of 60 clinical samples were collected from hospital clinical cases. Training samples were sent to the pre-training language model of Chinese Bert for training to generate intelligent diagnostic module. Simultaneously, a mathematical algorithm was developed to generate inferential digraphs. In order to evaluate the performance of the model, the values of accuracy, F1 score, Mse, Loss and other indicators were calculated for model training and testing. And the confusion matrices and ROC curves were plotted to estimate the predictive ability of the model. The novel model was also compared with RF and XGBOOST. And some instances of inferential digraphs with the model were displayed and analyzed. It may be a new attempt to solve the problem of interpretable and inferential intelligent models in the field of artificial intelligence on medical diagnosis of TCM.

Oral Administration of Fermented Milk from Co-Starter Containing Lactobacillus plantarum Y44 Shows an Ameliorating Effect on Hypertension in Spontaneously Hypertensive Rats.

Fermented dairy foods such as yogurt exhibit some beneficial effects on consumers, including relieving the symptoms of hypertension. This study aims to obtain fermented dairy products from a co-starter that have a great flavor and the auxiliary function of reducing blood pressure after longtime consumption. Commercial starter cultures composed of Lactobacillus delbrueckii subsp. bulgaricus CICC 6047 and Streptococcus thermophilus CICC 6038 were combined with Lactobacillus plantarum strains Y44, Y12, and Y16, respectively, as a combined starter culture to ferment the mixed milk of skim milk and soybean milk. The fermented milk produced using the combined starter culture mixed with L. plantarum Y44 showed an angiotensin-converting-enzyme (ACE) inhibitory activity (53.56 ± 0.69%). Some peptides that regulate blood pressure were released in the fermented milk, such as AMKPWIQPK, GPVRGPFPII, LNVPGEIVE, NIPPLTQTPV, and YQEPVL. In spontaneously hypertensive rat (SHR) oral-administration experiments compared with the gavage unfermented milk group, the gavage feeding of SHRs with the fermented milk produced using the combined starter culture mixed with L. plantarum Y44 significantly reduced the blood pressure of the SHRs after long-term intragastric administration, shown with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreasing by 23.67 ± 2.49 mmHg and 15.22 ± 2.62 mmHg, respectively. Moreover, the abundance of short-chain fatty acids (SCFA), bacterial diversity in the gut microbiota, and SCFA levels including acetic acid, propionic acid, and butyric acid in the feces of the SHRs were increased via oral administration of the fermented milk produced using the combined starter culture containing L. plantarum Y44. Furthermore, the ACE-angiotensin II (Ang II)-angiotensin type 1 (AT 1) axis was downregulated, the angiotensin-converting-enzyme 2 (ACE 2)-angiotensin(1-7) (Ang1-7)-Mas receptor axis of the SHRs was upregulated, and then the RAS signal was rebalanced. The fermented milk obtained from the combined starter culture shows the potential to be a functional food with antihypertension properties.

Ce/N @BC prepared based on plant metallurgy strategy: A novel activator of peroxymonosulfate for the degradation of sulfamethoxazole.

A novel carbon catalyst was created based on plant metallurgy strategy for organic pollutants removal. Plants rich in CeO2 NPs in water were used as carbon precursors and pyrolyzed with urea to obtain Ce/N co-doped carbon catalysts, which were used in the degradation of sulfamethoxazole (SMX) by active peroxymonosulfate (PMS). The results showed that the Ce/N @BC/PMS system achieved to 94.5% degradation of SMX in 40 min at a rate constant of 0.0602 cm-1. The activation center of PMS is widely dispersed Ce oxide nanocrystals, and CeO2 NPs promote the formation of oxygen centered PFR with enhanced catalytic ability and longer half-life. In addition, N-doping facilitates the transfer of π-electrons within the sp2 carbon of biochar, increasing active sites and thus improving PMS activation efficiency. The degradation process was contributed to by both radical and non-radical activation mechanisms including 1O2 and direct electron transfer, with O2•- serving as 1O2's precursor. Through the DFT calculations, LC-MS and toxicological analyses, the degradation pathway of pollutants and the toxicity changes throughout the entire degradation process were further revealed, indicating that the degradation of SMX could effectively reduce ecological toxicity.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for gastric cancer with intraoperative detection of limited peritoneal metastasis: a Phase II study of CLASS-05 trial.

Background: Systemic chemotherapy for gastric cancer with peritoneal metastasis has limited clinical benefit; for those with intraoperative detection of occult peritoneal metastasis, cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative treatment. However, the feasibility and effects of this modality and criteria for selecting suitable groups remain unclear. This study aimed to explore the safety and efficacy of laparoscopic cytoreductive surgery (L-CRS) followed by HIPEC in gastric cancer with limited peritoneal metastasis, and this study also aimed to determine the optimized cut-off of the peritoneal cancer index. Methods: Between March 2017 and November 2019, patients diagnosed with gastric cancer peritoneal metastases by using laparoscopy and the Sugarbaker peritoneal cancer index of ≤12 were eligible for inclusion. All patients received L-CRS (including gastrectomy with D2 lymph node dissection) and resection of visible peritoneal metastasis, followed by post-operative HIPEC, and systemic chemotherapy. The primary end points were median progression-free survival and median survival time, and the secondary outcomes were morbidity and mortality within 30 days after surgery. Results: Thirty patients were eligible for analysis, of whom 19 (63.3%) were female, and the overall mean age was 53.0 years. The post-operative morbidity was 20% and the severe complication rate was 10%. The median survival time was 27.0 months with a 2-year overall survival rate of 52.3% and median progression-free survival was 14.0 months with a 2-year progression-free survival of 30.4%. Conclusions: L-CRS followed by HIPEC can be safely performed for gastric cancer with limited peritoneal metastasis and potential survival benefits.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway.

BACKGROUND: Development of end-stage renal disease is predominantly attributed to diabetic nephropathy (DN). Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue. Nevertheless, the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain. AIM: To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism. METHODS: Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk. Subsequently, blood and urine indexes were assessed, along with examination of renal tissue pathology. Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin, periodic acid-Schiff, Masson's trichrome, and Sirius-red. Additionally, high-glucose culturing was conducted on the RAW 264.7 cell line, treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h. In both in vivo and in vitro settings, quantification of inflammation factor levels was conducted using western blotting, real-time qPCR and ELISA. RESULTS: In db/db mice, administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis. Notably, we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin, along with a decrease in expressions of inflammatory cytokine-related factors. Furthermore, myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha, interleukin-6, and interluekin-1ß induced by high glucose in RAW 264.7 cells. Additionally, myricetin modulated the M1-type polarization of the RAW 264.7 cells. Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin. The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002. CONCLUSION: This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer.

BACKGROUNDThe tumor immune microenvironment can provide prognostic and therapeutic information. We aimed to develop noninvasive imaging biomarkers from computed tomography (CT) for comprehensive evaluation of immune context and investigate their associations with prognosis and immunotherapy response in gastric cancer (GC).METHODSThis study involved 2,600 patients with GC from 9 independent cohorts. We developed and validated 2 CT imaging biomarkers (lymphoid radiomics score [LRS] and myeloid radiomics score [MRS]) for evaluating the IHC-derived lymphoid and myeloid immune context respectively, and integrated them into a combined imaging biomarker [LRS/MRS: low(-) or high(+)] with 4 radiomics immune subtypes: 1 (-/-), 2 (+/-), 3 (-/+), and 4 (+/+). We further evaluated the imaging biomarkers' predictive values on prognosis and immunotherapy response.RESULTSThe developed imaging biomarkers (LRS and MRS) had a high accuracy in predicting lymphoid (AUC range: 0.765-0.773) and myeloid (AUC range: 0.736-0.750) immune context. Further, similar to the IHC-derived immune context, 2 imaging biomarkers (HR range: 0.240-0.761 for LRS; 1.301-4.012 for MRS) and the combined biomarker were independent predictors for disease-free and overall survival in the training and all validation cohorts (all P < 0.05). Additionally, patients with high LRS or low MRS may benefit more from immunotherapy (P < 0.001). Further, a highly heterogeneous outcome on objective response ​rate was observed in 4 imaging subtypes: 1 (-/-) with 27.3%, 2 (+/-) with 53.3%, 3 (-/+) with 10.2%, and 4 (+/+) with 30.0% (P < 0.0001).CONCLUSIONThe noninvasive imaging biomarkers could accurately evaluate the immune context and provide information regarding prognosis and immunotherapy for GC.

The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis.

BACKGROUND: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. RESULTS: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. CONCLUSION: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. CLINICAL RELEVANCE: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.

Fabricating an adsorbent and micro-nano bubble catalyst through confining maghemite in the ß cage of NaY zeolite.

This work reports the ion exchange fabrication of maghemite (γ-Fe2O3) modified NaY zeolite (Fe2O3@Y) with bifunction of adsorption and catalysis. The Fe3+ successfully replaced the Na+ in the ß cage of zeolite in the ion exchange process and coordinated with framework oxygens to form magnetic γ-Fe2O3. Therefore, most of the γ-Fe2O3 particles were confined in the ß cages, which resulted in the high dispersal and stability of the catalyst. The Fe2O3@Y could remove methylene blue (MB) model pollutants up to 59.02 and 61.47% through the adsorption and catalysis process, respectively. The hydrogen bond between the OH- ions around the Fe2O3@Y surface and the N and O presented in the MB molecules enabled the chemical adsorption to MB, which accorded with the pseudo-second-order kinetic model. Further, the H+ existed in the solution and the ß cage of zeolite promoted the collapse of micro-nano bubbles (MNBs). Then, the γ-Fe2O3 catalyst would be activated by high temperature and oxidated OH- to produce hydroxyl radicals for pollutant degradation. Thus, pollutant removal was attributed to the combined effects of adsorption and catalysis in the Fe2O3@Y + MNB system. In this work, the Fe2O3@Y was demonstrated as a potentially magnetic adsorbent or MNB catalyst for wastewater treatment.

microRNA-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation.

BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.

Hypericumliboense (Hypericaceae), a new species from Guizhou, China.

Hypericumliboense M.T.An & T.R.Wu, sp. nov. (Hypericaceae) is a newly described species found in the Maolan National Nature Reserve of Guizhou Province, where it grows in rocky habitats without soil on karst mountain tops. In this study, key morphological characters were compared between the new species and the other known Hypericum species of Hypericaceae. DNA sequences were extracted from the leaves of the new species, with nuclear gene sequences (ITS) generated to reconstruct phylogenetic trees and describe its phylogenetic position in relation to other species of Hypericum. Our results show that the proposed new species has the typical characteristics of the genus Hypericum in morphology being similar to Hypericummonogynum, but differing in its sessile and semi-clasped leaves, long elliptical to long circular leaf blades, thickly papery to thinly leathery, with entire and wavy leaf margins. The abaxial side of the leaves is covered with white powder, giving them a grey-white appearance. The main lateral veins of the leaves are 8-15-paired, and the midvein on both sides is convex. The main lateral veins and midvein branch are conspicuous, with tertiary venation forming a network on the leaf surface and appearing prominently sunken. The inflorescences are 1-3-flowered, with a large calyx and conspicuous veins. The molecular phylogenetic analysis (PP = 1.00) provided substantial evidence for the proposition of H.liboense as a new species within Hypericum. Morphological and molecular evidence is presented, corroborating the proposition of the new species, including a comprehensive account of the distinctive morphological attributes of H.liboense, along with its key distinguishing features from similar species.

AI-enhanced chemical paradigm: From molecular graphs to accurate prediction and mechanism.

The development of accurate and interpretable models for predicting reaction constants of organic compounds with hydroxyl radicals is vital for advancing quantitative structure-activity relationships (QSAR) in pollutant degradation. Methods like molecular descriptors, molecular fingerprinting, and group contribution methods have limitations, as traditional machine learning struggles to capture all intramolecular information simultaneously. To address this, we established an integrated graph neural network (GNN) with approximately 12 million learnable parameters. GNN represents atoms as nodes and chemical bonds as edges, thus transforming molecules into a graph structures, effectively capturing microscopic properties while depicting atom connectivity in non-Euclidean space. Our datasets comprise 1401 pollutants to develop an integrated GNN model with Bayesian optimization, the model achieves root mean square errors of 0.165, 0.172, and 0.189 on the training, validation, and test datasets, respectively. Furthermore, we assess molecular structure similarity using molecular fingerprint to enhance the model's applicability. Afterwards, we propose a gradient weight mapping method for model explainability, uncovering the key functional groups in chemical reactions in artificial intelligence perspective, which would boost chemistry through artificial intelligence extreme arithmetic power.

Insights into the potential applications of permanganate/peroxymonosulfate systems: enhancement via amorphous MnO2, effects of water matrices, and optimization using response surface methodology.

In this study, we developed a novel self-catalytic oxidation system involving peroxymonosulfate (PMS) and permanganate (KMnO4), named as CUPP, to efficiently mineralize sulfamethoxazole (SMX) in groundwater. It was found that amorphous MnO2 derived from the in situ reduction of KMnO4 can directly adsorb HSO5-, a complex hydroxyl group, mediate the internal disproportionation reaction of HSO5- with the manganese complex, and effectively activate PMS, thereby promoting the oxidation of SMX and its degradation intermediates through sulfonate radiation. Furthermore, by using electron spin resonance (EPR), HPLC/MS full scan, and response surface methodology, the coexistence of HO˙, SO4-˙, O2-˙, 1O2, and active chlorine (Cl2, HOCl) in the CUPP system was confirmed. A total of 24 intermediate products were detected, and four possible degradation pathways were identified for SMX. In addition, it was found that the CUPP system has a strong impact resistance to pH variations, groundwater anions, and natural organic matter stress. Undoubtedly, the CUPP system presents an innovative approach for the degradation of various emerging organic pollutants in groundwater.