Novel use of structural equation modeling to examine the development of a framework of patient-centered two-way referral systems for building digital subjective well-being healthcare: A cross-sectional survey in Central China.

Background: Digital health technologies are progressively assuming significant roles in aspects encompassing in-hospital management, patient-centered design, and tiered referral systems. Nevertheless, current studies do not involve exploration into the potential value and mechanisms of digital health in a patient-centered context. This study aimed to explore the development of a framework of comprehensive, evidence-based digital health technologies for the construction of welfare-oriented healthcare. Methods: From March to June 2023, a cross-sectional online study was performed, involving 335 respondents with prior referral experiences hailing from the Central China region. Data on welfare-oriented healthcare factors (clinical pathway management, medical structure configuration, healthcare service accessibility, two-way referrals) underwent factor analysis in advance, and correlation between these factors and their association with two-way referrals was evaluated by testing for direct and indirect (mediating) effects. Results: Firstly, there existed a significant positive correlation between integrative medical indicators and welfare-centered healthcare (ß = 0.02-0.16, p < 0.05). Furthermore, two-way referral had an direct association with integrative medical parameters and the welfare healthcare service system (ß = 0.15-0.31, p < 0.05), but exerted a partial mediatory function in the welfare healthcare service system (ß = 0.005-0.021, α < 0.05). Two-way referrals partially mediate the integrated medical indicators, mainly through direct effects, while also providing complementary support. Clinical pathways, medical structure, and accessibility are closely linked to welfare healthcare and significantly influence healthcare quality. Thus, improving these factors should be prioritized. Conclusion: This study proposes a method combining integrated evaluation indicators with pathway mechanism design. This pathway mechanism design includes key steps such as patient registration, information extraction, hospital allocation or referral, diagnosis and treatment, rehabilitation plan monitoring, service feedback, and demand resolution. This design aims to change patients' intentions in seeking healthcare, thereby increasing their acceptance of bidirectional referrals, and ultimately enhancing the effectiveness and realization of welfare healthcare.

FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.

PURPOSE: Cisplatin is a low-cost clinical anti-tumor drug widely used to treat solid tumors. However, its use could damage cochlear hair cells, leading to irreversible hearing loss. Currently, there appears one drug approved in clinic only used for reducing ototoxicity associated with cisplatin in pediatric patients, which needs to further explore other candidate drugs. METHODS: Here, by screening 1967 FDA-approved drugs to protect cochlear hair cell line (HEI-OC1) from cisplatin damage, we found that Tedizolid Phosphate (Ted), a drug indicated for the treatment of acute infections, had the best protective effect. Further, we evaluated the protective effect of Ted against ototoxicity in mouse cochlear explants, zebrafish, and adult mice. The mechanism of action of Ted was further explored using RNA sequencing analysis and verified. Meanwhile, we also observed the effect of Ted on the anti-tumor effect of cisplatin. RESULTS: Ted had a strong protective effect on hair cell (HC) loss induced by cisplatin in zebrafish and mouse cochlear explants. In addition, when administered systemically, it protected mice from cisplatin-induced hearing loss. Moreover, antitumor studies showed that Ted had no effect on the antitumor activity of cisplatin both in vitro and in vivo. RNA sequencing analysis showed that the otoprotective effect of Ted was mainly achieved by inhibiting phosphorylation of ERK. Consistently, ERK activator aggravated the damage of cisplatin to HCs. CONCLUSION: Collectively, these results showed that FDA-approved Ted protected HCs from cisplatin-induced HC loss by inhibiting ERK phosphorylation, indicating its potential as a candidate for preventing cisplatin ototoxicity in clinical settings.

Causal relationship between inflammatory cytokines and autoimmune thyroid disease: a bidirectional two-sample Mendelian randomization analysis.

Background: Autoimmune thyroid disease (AITD) ranks among the most prevalent thyroid diseases, with inflammatory cytokines playing a decisive role in its pathophysiological process. However, the causal relationship between the inflammatory cytokines and AITD remains elusive. Methods: A two-sample Mendelian randomization (MR) analysis was performed to elucidate the causal connection between AITD and 41 inflammatory cytokines. Genetic variations associated with inflammatory cytokines were sourced from the FinnGen biobank, whereas a comprehensive meta-analysis of genome-wide association studies (GWASs) yielded data on Graves' disease (GD) and Hashimoto thyroiditis. Regarding the MR analysis, the inverse variance-weighted, MR-Egger, and weighted median methods were utilized. Additionally, sensitivity analysis was conducted using MR-Egger regression, MR-pleiotropy residual sum, and outliers. Results: Seven causal associations were identified between inflammatory cytokines and AITD. High levels of tumor necrosis factor-ß and low levels of stem cell growth factor-ß were indicative of a higher risk of GD. In contrast, high levels of interleukin-12p70 (IL-12p70), IL-13, and interferon-γ and low levels of monocyte chemotactic protein-1 (MCP-1) and TNF-α suggested a higher risk of HD. Moreover, 14 causal associations were detected between AITD and inflammatory cytokines. GD increases the levels of macrophage inflammatory protein-1ß, MCP-1, monokine induced by interferon-γ (MIG), interferon γ-induced protein 10 (IP-10), stromal cell-derived factor-1α, platelet-derived growth factor BB, ß-nerve growth factor, IL-2ra, IL-4, and IL-17 in blood, whereas HD increases the levels of MIG, IL-2ra, IP-10, and IL-16 levels. Conclusion: Our bidirectional MR analysis revealed a causal relationship between inflammatory cytokines and AITD. These findings offer valuable insights into the pathophysiological mechanisms underlying AITD.

Stable Perovskite Quantum Dots Light-Emitting Diodes with Efficiency Exceeding 24.

Perovskite nanocrystals for light-emitting diodes are often synthesized by uncontrollable metathesis reactions, suffering from low product yield, nonuniform growth, and poor stability. Herein, by controlling the nucleation kinetics with high dissociation constant (Ka or Kb) acids or bases, homogenous one-route nucleation of perovskite nanocrystals is achieved as the cluster intermediates are eliminated. The stable, shape uniform, and narrow size distribution green nanocrystals are synthesized. The perovskite nanocrystal film exhibites excellent stability in 80% humidity air with only a 10% photoluminescence intensity drop after 16 h. Efficient and stable electroluminescence is demonstrated with an FWHM of 16 nm at 517 nm. The green devices shows a peak EQE of 24.13% with a lifetime T50 of 54 min at 10 000 cd m-2 .

Interesting influence of Al2O3 on the catalytic stability of Co2P, MoP and CoMoP catalysts for dry reforming of methane.

Interestingly, the metal-support interaction (MSI) influence of different metal phosphides on catalytic stability might be different in dry reforming of methane (DRM). After being supported on Al2O3, there was a rise, decline and no change in the catalytic stability of CoMoP, MoP and Co2P, respectively. This was probably because the MSI can tune the structural stability, methane dissociation ability and oxidation resistance ability of metal phosphides, which were the key factors that determined their catalytic stability.

Effect of megarectum on postoperative defecation of female patients with congenital rectovestibular fistula or rectoperineal fistula.

Background: To assess the effect of megarectum on postoperative defecation of female patients with congenital rectovestibular fistula or rectoperineal fistula. Methods: From March 2013 to February 2021, 74 female patients with congenital rectovestibular fistula or rectoperineal fistula were treated. The age of patients ranged from 3 months to 1 year. Barium enema and spinal cord MRI were performed in all children. 4 patients were removed from the study because of spinal cord and sacral agenesis. Finally, 70 patients underwent one-stage anterior sagittal anorectoplasty (ASARP). Anal endoscopy and anorectal pressure measurement were performed 1 year after surgery. All patients were divided into two groups depending on the presence of megarectum (+) and (-) and observed for constipation and anal sphincter function. Results: 16 patients (4 months to 1 year) were complicated with megarectum, and 5 patients (3 months to 9 months) were without megarectum. The incision infection was seen in 3 patients. All patients were followed up for 1 year to 5 years. Fecal soiling was seen in 2 patients and constipation in 14 patients. Among 16 patients with megarectum, soiling was seen in 1 patient and the constipation in 12 patients. Among 54 patients without megarectum, soiling was seen in 1 patient and constipation in 2 patients. There was a significant difference in the incidence of postoperative constipation between the two groups (megarectum (+) 75% vs. megarectum (-) 3.7% (P < 0.05)). However, there was no significant difference in the score of anal sphincters between the two groups (P < 0.05). And there was no significant difference in anal resting pressure (P = 0.49) and length of anal high pressure area (P = 0.76). 7 patients with constipation and megarectum acquired normal anal function after the dilated rectum was resected. Conclusion: Megarectum increases the possibility of difficult postoperative defecation in the patients with congenital rectovestibular fistula or rectoperineal fistula. However, constipation was not associated with ASARP postoperative effects on sphincter function. Resection of megarectum is helpful to the improvement of constipation.

A novel lnc-LAMC2-1:1 SNP promotes colon adenocarcinoma progression by targeting miR-216a-3p/HMGB3.

Single nucleotide polymorphisms (SNPs) was associated with altering the secondary structure of long non-coding RNA (lncRNA). Increasing reports showed that lnc-LAMC2-1:1 SNP played an important role in cancer development and invasion. This study is to elucidate the molecular function of lnc-LAMC2-1:1 SNP rs2147578 promoting tumor progression in colon adenocarcinoma (COAD). In this study, we found that the lnc-LAMC2-1:1 SNP rs2147578 was upregulated in COAD cell lines. Furthermore, lnc-LAMC2-1:1 SNP rs2147578 promoted colon cancer migration, invasion, and proliferation. Interestingly, lnc-LAMC2-1:1 SNP rs2147578 positively regulated HMGB3 expression via miR-216a-3p in colon cancer cells. Functional enrichment analysis showed that targeting genes of miR-216a-3p were enriched in regulating the pluripotency of stem cells, MAPK signaling pathway, TNF signaling pathway, neurotrophin signaling pathway, relaxin signaling pathway, and FoxO signaling pathway. Tumor Immune Estimation Resource (TIMER) database revealed that there was a significantly positive correlation between HMGB3 expression and the infiltration of CD8+ T cells, B cells, neutrophils, macrophages, and CD4+ T cells. Finally, HMGB3 overexpression was validated in external data. In conclusions, lnc-LAMC2-1:1 SNP rs2147578 was involved in promoting COAD progression by targeting miR-216a-3p/HMGB3, and this study will provide a novel molecular target for COAD.

Circularly Polarized Luminescent Eu4(LR)4 Cage for Enantiomeric Excess and Concentration Simultaneous Determination of Chiral Diamines.

Undoubtably, it is challenging to simultaneously determine the identity, enantiomeric excess (ee), and total concentration of an enantiomer by just one optical measurement. Herein, we design a chiral tetrahedron Eu4(LR)4 with circularly polarized luminescence (CPL), which presents highly selective/stereoselective, rapid, and "turn-on" CPL response to chiral diamines, rather than the monoamino compounds, such as monoamines or amino alcohols. By recording the left- and right-CPL intensities of the Eu3+ ion at 591 nm, the enantiomeric composition and concentration of chiral diamines can be simultaneously determined by monitoring the glum value and total emission intensity (IL + IR), respectively. Spectroscopy analyses demonstrate that the variations of glum depend on the inversion and maintenance of configuration around the Eu3+ ion (Δ â†” Λ), while the "turn-on" response arises from the raising of the T1 state of the ligand. The molecule/electron structural variations are proposed from the synergetic supramolecular interactions of NH2 groups with pendant diols and trifluoroacetyl groups.

Computational study on new natural compound inhibitors of Traf2 and Nck-interacting kinase (TNIK).

Traf2 and Nck-interacting kinase (TNIK) is the downstream molecule of Wnt/ß-catenin signal pathway. As the activation kinase of ß-catenin/T-cell factor 4 transcription complex, it can fully activate Wnt signalling and promote the growth and invasion of tumor cells. We conducted computer-assisted virtual screening and a series of analyses to find potential inhibitors of TNIK. First, LibDock was used for molecular docking of natural small molecules. Then, ADME (Adsorption, Distribution, Metabolism and Excretion) analysis and toxicity prediction were performed on the top 80 small molecules which have higher scores. Additionally, in order to further determine the affinity and binding mechanism of TNIK-ligands, we analyzed the pharmacophores and used CDOCKER for more accurate molecular docking. Last but not least, molecular, dynamics simulation was used to evaluate the stability of receptor-ligand complexes in natural environment. The results showed that natural small molecules (ZINC000040976869 and ZINC000008214460) had high affinity and low interaction energy with TNIK. They were predicted to have excellent pharmacological properties, such as high plasma protein binding capacity and water solubility, no hepatotoxicity, no blood-brain barrier permeability and tolerant with cytochrome P450 2D6 (CYP2D6). In addition, they have less rodent carcinogenicity, AMES mutagenicity, and developmental toxicity potential. Molecular dynamics simulations showed that the two compounds could achieve the stability of potential energy and Root-Mean-Square Deviation (RMSD) at different time nodes. This study proves that ZINC000040976869 and ZINC000008214460 are ideal lead compounds with inhibition targeting to TNIK. These compounds provide valuable ideas and information for the development of new colorectal cancer targeting drugs.

Dioscin ameliorates slow transit constipation in mice by up-regulation of the BMP2 secreted by muscularis macrophages.

Objectives: The loss of enteric neurons has been shown to be a major cause of slow transit constipation (STC). Gut microbiota and muscularis macrophages (MMs) are associated with the enteric nervous system (ENS) development and gastrointestinal (GI) motility. This study aimed to investigate whether Dioscin (DIO) increased GI motility and inhibited neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment. Materials and Methods: The STC model was established by loperamide. The alteration of the gut microbiota was analyzed by 16S rDNA sequencing. The longitudinal muscle and myenteric plexus (LMMP) from the colon were prepared for flow cytometry, immunofluorescence, western blot, and qRT-PCR. Results: DIO increased the stool number, stool water content and shortened whole gut transit time, helped to recover the gut microbial diversity and microbiota community structure, and increased the abundance of Muribaculaceae in STC mice. Compared with the STC group, the number of MMs and the level of the iNOS, IL-6, and TNFα genes were significantly decreased following DIO treatment. Moreover, DIO may increase the number of HuC/D+ neurons per ganglion by up-regulating the BMP2 secreted by MMs and activating the BMP2/p-Smad1/5/9 signaling pathway. Furthermore, the level of excitatory neurotransmitter AchE in colon tissues exhibited a substantial increase in the DIO group. However, the level of inhibitory neurotransmitter VIP was markedly decreased. Conclusion: Our results provide that DIO increases GI motility and inhibits neuron loss by modulating gut microbiota profile, improving inflammation in the ENS microenvironment and up-regulating the BMP2 secreted by MMs.

Asymmetric induction in quadruple-stranded europium(III) helicates and circularly polarized luminescence.

Chiral supramolecular lanthanide-helicates are regarded as promising chiroptical materials due to their combination of ground and excited state chirality and special luminescence properties from Ln3+, named circularly polarized luminescence (CPL). However, the sophisticated and costly asymmetric syntheses decelerate their research progress. Herein, a chiral induction strategy is employed to break the racemic equilibrium of lanthanide helicate by the formation of a compact ion pair. The synthesized chiral guanidine cation ((R/S)-HG) helps to effectively transfer chirality to anionic quadruple-stranded helicate by electrostatic, H bonds, and multiple C-H⋯F and N-H⋯F interactions. The diastereoselective control was confirmed by X-ray crystallography and CD and CPL spectroscopy, where (S)-HG prefers to bind a P (ΔΔ) helical enantiomer, in contrast a M helicate for (R)-HG. Additionally, the inconsistency of CD and CPL spectra in assessing the perturbation of a racemic equilibrium discloses their complementary advantages on monitoring molecular chirality. In the case of diastereomeric enrichment equilibrium, three pairs of helicates show high luminescence quantum yields of 42%-54%, and large |glum| with the values of 0.137-0.266. This work provides an effective strategy to synthesize excellent CPL materials based on racemic lanthanide helicate.

Based on Network Pharmacology and Gut Microbiota Analysis to Investigate the Mechanism of the Laxative Effect of Pterostilbene on Loperamide-Induced Slow Transit Constipation in Mice.

Background: Pterostilbene (PTE) is a natural polyphenol compound that has been proven to improve intestinal inflammation, but its laxative effect on slow transit constipation (STC) has never been studied. This study aims to investigate the laxative effect of PTE on loperamide (LOP)-induced STC mice and its influence on intestinal microbes through a combination of network pharmacological analysis and experimental verification. Material and Methods: PTE was used to treat LOP-exposed mice, and the laxative effect of PTE was evaluated by the total intestinal transit time and stool parameters. The apoptosis of Cajal interstitial cells (ICCs) was detected by immunofluorescence. The mechanism of PTE's laxative effect was predicted by network pharmacology analysis. We used western blot technology to verify the predicted hub genes and pathways. Malondialdehyde (MDA) and GSH-Px were tested to reflect oxidative stress levels and the changes of gut microbiota were detected by 16S rDNA high-throughput sequencing. Results: PTE treatment could significantly improve the intestinal motility disorder caused by LOP. Apoptosis of ICCs increased in the STC group, but decreased significantly in the PTE intervention group. Through network pharmacological analysis, PTE might reduce the apoptosis of ICCs by enhancing PI3K/AKT and Nrf2/HO-1 signaling, and improve constipation caused by LOP. In colon tissues, PTE improved the Nrf2/HO-1 pathway and upregulated the phosphorylation of AKT. The level of MDA increased and GSH-Px decreased in the STC group, while the level of oxidative stress was significantly reduced in the PTE treatment groups. PTE also promoted the secretion of intestinal hormone and restored the microbial diversity caused by LOP. Conclusion: Pterostilbene ameliorated the intestinal motility disorder induced by LOP, this effect might be achieved by inhibiting oxidative stress-induced apoptosis of ICCs through the PI3K/AKT/Nrf2 signaling pathway.

Hepatic Lesion of Mucosa-Associated Lymphoid Tissue Lymphoma Revealed by Al18F-NOTA-FAPI-04 PET/CT.

ABSTRACT: A middle-aged man was newly diagnosed with mucosa-associated lymphoid tissue lymphoma with secondary liver involvement. The hepatic lesion was not shown on FDG PET/CT but FAPI (fibroblast-activated protein inhibitor) PET/CT, which revealed abnormal FAPI accumulation. This case demonstrated that FAPI PET/CT might provide value in hepatic mucosa-associated lymphoid tissue lymphoma.

Nickel clusters accelerating hierarchical zinc indium sulfide nanoflowers for unprecedented visible-light hydrogen production.

As a typical two-dimensional (2D) metal chalcogenides and visible-light responsive semiconductor, zinc indium sulfide (ZnIn2S4) has attracted much attention in photocatalysis. However, the high recombination rate of photogenerated electrons and holes seriously limits its performance for hydrogen production. In this work, we report in-situ photodeposition of Ni clusters in hierarchical ZnIn2S4 nanoflowers (Ni/ZnIn2S4) to achieve unprecedented photocatalytic hydrogen production. The Ni clusters not only provide plenty of active sites for reactions as evidenced by in-situ photoluminescence measurement, but also effectively accelerate the separation and migration of the photogenerated electrons and holes in ZnIn2S4. Consequently, the Ni/ZnIn2S4 composites exhibit good stability and reusability with highly enhanced visible-light hydrogen production. In particular, the best Ni/ZnIn2S4 photocatalyst exhibits an unprecedented hydrogen production rate of 22.2 mmol·h-1·g-1, 10.6 times that of the pure ZnIn2S4 (2.1 mmol·h-1·g-1). And its apparent quantum yield (AQY) is as high as 56.14% under 450 nm monochromatic light. Our work here suggests that depositing non-precious Ni clusters in ZnIn2S4 is quite promising for the potential practical photocatalysis in solar energy conversion.

Al18F-NOTA-FAPI-04 Outperforms 18F-FDG PET/CT in Identifying the Primary Lesion and Rare Metastases From Gastric Cancer.

ABSTRACT: A 45-year-old woman with gastric cancer underwent FDG PET/CT for initial staging. However, the primary and the metastatic lesions were observed with low or no FDG uptake. Then, the patient underwent fibroblast-activated protein inhibitor PET/CT 2 days later, which demonstrated more lesions and much higher tumor-to-background contrast than FDG PET/CT did.

Perovskite Quantum Dots with Ultralow Trap Density by Acid Etching-Driven Ligand Exchange for High Luminance and Stable Pure-Blue Light-Emitting Diodes.

The research on metal halide perovskite light-emitting diodes (PeLEDs) with green and infrared emission has demonstrated significant progress in achieving higher functional performance. However, the realization of stable pure-blue (≈470 nm wavelength) PeLEDs with increased brightness and efficiency still constitutes a considerable challenge. Here, a novel acid etching-driven ligand exchange strategy is devised for achieving pure-blue emitting small-sized (≈4 nm) CsPbBr3 perovskite quantum dots (QDs) with ultralow trap density and excellent stability. The acid, hydrogen bromide (HBr), is employed to etch imperfect [PbBr6 ]4- octahedrons, thereby removing surface defects and excessive carboxylate ligands. Subsequently, didodecylamine and phenethylamine are successively introduced to bond the residual uncoordinated sites of the QDs and attain in situ exchange with the original long-chain organic ligands, resulting in near-unity quantum yield (97%) and remarkable stability. The QD-based PeLEDs exhibit pure-blue electroluminescence at 470 nm (corresponding to the Commission Internationale del'Eclairage (CIE) (0.13, 0.11) coordinates), an external quantum efficiency of 4.7%, and a remarkable luminance of 3850 cd m-2 , which is the highest brightness reported so far for pure-blue PeLEDs. Furthermore, the PeLEDs exhibit robust durability, with a half-lifetime exceeding 12 h under continuous operation, representing a record performance value for blue PeLEDs.

Ancillary ligand modulated stereoselective self-assembly of triple-stranded Eu(iii) helicate featuring circularly polarized luminescence.

Creating optically pure metal assemblies is a hot research topic in the realms of chiral supramolecules. Here, three new triple-stranded europium(iii) helicates Eu2L3(L')2 [L = 4,4'-bis(4,4,4-trifluoro-1,3-dioxobutyl)diphenyl sulphide; L' = 1,10-phenanthroline (Phen) or R/S-2,2'-bis(diphenylphosphinyl)-1,1'-binaphthyl (R/S-BINAPO)] were synthesized in order to investigate the effects of ancillary ligands on controlling the stereoselective self-assembly of lanthanide helicates. X-ray single crystal structure analysis showed that Eu2L3(Phen)2 crystalized in an achiral space group P1̄ with the equivalent amount of P and M helicates in one single cell. The isolated Eu2L3(S-BINAPO)2 and Eu2L3(R-BINAPO)2 were verified to be enantiopure by 1H, 19F, 31P NMR and DOSY NMR analyses. Additionally, the mirror-image CD spectra also demonstrated the successful syntheses of the enantiomers and the presence of an effective chirality transformation from BINAPO to achiral L. Furthermore, the perfect mirror-image circularly polarized luminescence (CPL) spectra of Eu2L3(S-BINAPO)2 and Eu2L3(R-BINAPO)2 indicated the existence of the excited state chirality of the Eu3+ center associated with |g lum| values reaching 0.112. In addition, the photophysical properties of three helicates were also discussed.

4,5-Dioxo-imidazolinium Cation Activation of 1-Acyl-1-carbamoyl Oximes: Access to Cyanoformamides Using Dichloroimidazolidinedione.

Cyanoformamides are prevalent as versatile building blocks for accessing synthetically useful intermediates and biologically active compounds. The development of a milder, simpler, and more efficient approach to cyanoformamides is nontrivial. Herein, we demonstrate the effectiveness of 4,5-dioxo-imidazolinium cation activation for transforming 1-acyl-1-carbamoyl oximes to cyanoformamides. By making use of the readily available and highly modifiable dichloroimidazolidinediones (DCIDs), this novel method of activation offers reactivity remarkably greater than that of other reported protocols, exhibits a high functional group compatibility with mild conditions, and could be scaled up easily. More than 30 examples are demonstrated with good to excellent yields in short reaction times. This research not only provides a mild and efficient alternative approach to assembling a portfolio of cyanoformamides but also extends the dichloroimidazolidinedione-mediated chemistry to encompass the C-C bond cleavage reaction.

Novel synthesis of a NiMoP phosphide catalyst in a CH4-CO2 gas mixture.

NiMo bimetallic phosphide was synthesized from its corresponding oxidic precursor in a 1 : 1 CH4 : CO2 gas mixture for the first time. The in situ synthesized NiMoP phase in the feed for CH4-CO2 reforming can exhibit a higher activity compared to the one prepared in H2.