Simulation of Binder Jetting and Analysis of Magnesium Alloy Bonding Mechanism.

Binder jetting (3DP) is a kind of additive manufacturing at room temperature and atmospheric environment, which can reduce the risk of magnesium alloy forming. Magnesium alloy powder is bonded to a certain structure by a binder, so the appropriate binder is very important in 3DP. In this study, according to the characteristics of magnesium alloy, a simple and easy-to-obtain water-based low-molecular alcohol binder was used to reduce the difficulty of magnesium alloy 3DP. Additionally, we use COMSOL Multiphysics simulation software to establish a simulation model of the movement and deposition process of the binder. The results show that the increase in jet velocity will increase the quality and saturation of droplets. More importantly, the larger the jet velocity is, the larger the spreading width of the binder droplet after impacting the powder bed, which seriously affects the dimensional accuracy of the green part. In addition, lower binder saturation will weaken the formation of interparticle bonding neck and cannot form a stable structure. Furthermore, we analyzed the bond reactants of the binder and magnesium alloy powder, which eventually decompose into MgO, and the experimental results show that the final sintered sample has considerable performance.

Myasthenia gravis with tongue muscle atrophy: A case series.

Here, we presented 6 patients who were admitted to our institution and diagnosed as myasthenia gravis (MG) with tongue muscle atrophy. All these 6 patients developed symptoms of bulbar muscle weakness in acetylcholine receptor antibodies positive MG (AChR-MG) (3/6), muscle-specific receptor tyrosine kinase antibodies positive MG (MuSK-MG) (1/6), and sero-negative MG (2/6). Most of patients had "triple-furrowed" tongue except for patient 2 with irregular atrophy of tongue muscle. Tongue muscle atrophy occurs in patients with MuSK-MG, AChR-MG, and sero-negative MG. Atrophied tongue muscles of five patients with MG were reversible after immunotherapy.

Pentacyclic triterpenoids as potential ACL inhibitors from the rare medicinal plant Semiliquidambar cathayensis.

An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.

Prognostic Significance of Preoperative and Postoperative Evaluation of Combined Tumor Markers for Patients With Colon Cancer.

BACKGROUND: The combined value of the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients with colon cancer (CC) is unclear. This study aimed to investigate the role of composite tumor markers in the prognosis of CC. METHODS: Patients who underwent curative resection of colon adenocarcinoma were enrolled. The tumor marker status before and after the operation was used to divide the patients into groups according to the number of tumor markers with abnormal expression, and recurrence-free survival (RFS) and overall survival (OS) of different groups were compared. The impact of changes in composite tumor markers in the perioperative period on outcomes was further explored. RESULTS: Ultimately, 531 patients were enrolled in the study. As the number of preoperative and postoperative elevated tumor markers increased, both RFS and OS rates became lower (both P<0.05). Further analysis revealed that the number of elevated tumor markers after resection can significantly affect the outcomes (both P<0.05). In patients with abnormal preoperative tumor markers, normalization of markers after surgery was a protective factor for prognosis (both P<0.05), and patients with postoperative elevated levels of both tumor markers had a 5.5-fold and 6-fold increase in the risk of recurrence and death. In addition, patients with elevated markers after surgery had a high risk of recurrence within 5 years after colectomy. CONCLUSIONS: Postoperative tumor markers had a better ability to differentiate postoperative outcomes in patients with CC than preoperative tumor markers. Patients whose tumor markers normalized after surgery had a better prognosis.

Multifunctional Material Building Blocks from Plant Pollen.

With its multifaceted nature, plant pollen serves not only as a key element in the reproductive cycle of seed plants but also as an influential contributor to environmental, human health, safety, and climate-related concerns. Pollen functions as a carrier of nutrients and organisms and holds a pivotal role in sustaining pollinator populations. Moreover, it is vital in ensuring the safety and quality of our food supply while presenting potential therapeutic applications. Pollen, often referred to as the diamond of the organic world due to its distinctive physical structures and properties, has been underappreciated from a material science and engineering standpoint. We propose adopting a more interdisciplinary and comprehensive approach to its study. Recent groundbreaking research has focused on the development of pollen-based building blocks that transform practically indestructible plant pollen into microgel, paper, and sponge, thereby unveiling numerous potential applications. In this review, we highlight the transformative potential of plant pollen as it is converted into a variety of building blocks, thereby unlocking myriad prospective applications through eco-friendly processing.

[Water-soluble Inorganic Ion Content of PM2.5 and Its Change Characteristics in Urban Area of Beijing in 2022].

To explore the content and variation characteristics of water-soluble ions of atmospheric fine particles (PM2.5) in a Beijing urban area and put forward the pollution prevention and control scheme, the water-soluble ions, gaseous precursors (SO2, NO2), and meteorological factors (temperature, RH) of PM2.5 in 2022 were analyzed and determined. The results showed that the water-soluble ions with the highest proportion in PM2.5 in the Beijing City urban area were NO3-, NH4+, and SO42-, accounting for 52.7% of PM2.5. The mass concentrations of PM2.5 and SNA were lower than the historical results, whereas the proportion of SNA, SOR, and NOR was higher than the historical results. This showed that the fine particulate matter pollution in Beijing has been significantly improved, but it still has strong secondary pollution characteristics. NO3-/SO42-(2.2) was higher than those of historical and nearby provinces and cities, reflecting the expanding influence of mobile sources. In terms of seasonal variation, PM2.5 showed the characteristic of high in autumn and low in summer. The proportion of NO3- was the highest in autumn, spring, and winter; the proportion of SO42- was the highest in summer; and the proportion of NH4+ changed little in each season. The seasonal variation rules of NOR and SOR were almost opposite, which reflected the difference in transformation factors between NOR and SOR. The main forms of SNA in the Beijing urban area were NH4NO3 and (NH4)2SO4. The neutralization degree of cations and anions was the highest in winter, the cation NH4+ was slightly insufficient in summer, and NH4+ was in excess in spring and autumn. The Beijing urban area was an ammonia-rich environment. In terms of pollution level, RH, particulate matter moisture, and water-soluble ions mass concentration all increased with the increase in pollution level, and SNA increased fastest, with its proportion in PM2.5 increasing first and then stabilizing, whereas the contribution rate of other water-soluble ions decreased gradually. In terms of spatial distribution, the mass concentration relationship of SNA at the central urban area and suburbs was NO3- > SO42- > NH4+, which reflected the pollution characteristics dominated by NO3-. The highest contribution rate of SNA to PM2.5 occurred in the eastern region, the central urban area, and the transmission point, indicating that the secondary reaction was relatively active in the central urban area and the eastern region, and the regional transport was also an important source of secondary ions.

Virtual reality-based cognitive-behavioural therapy for the treatment of anxiety in patients with acute myocardial infarction: a randomised clinical trial.

Background: The presence of mental health conditions is pervasive in patients who experienced acute myocardial infarction (AMI), significantly disrupting their recovery. Providing timely and easily accessible psychological interventions using virtual reality-based cognitive-behavioural therapy (VR-CBT) could potentially improve both acute and long-term symptoms affecting their mental health. Aims: We aim to examine the effectiveness of VR-CBT on anxiety symptoms in patients with AMI who were admitted to the intensive care unit (ICU) during the acute stage of their illness. Methods: In this single-blind randomised clinical trial, participants with anxiety symptoms who were admitted to the ICU due to AMI were continuously recruited from December 2022 to February 2023. Patients who were Han Chinese aged 18-75 years were randomly assigned (1:1) via block randomisation to either the VR-CBT group to receive VR-CBT in addition to standard mental health support, or the control group to receive standard mental health support only. VR-CBT consisted of four modules and was delivered at the bedside over a 1-week period. Assessments were done at baseline, immediately after treatment and at 3-month follow-up. The intention-to-treat analysis began in June 2023. The primary outcome measure was the changes in anxiety symptoms as assessed by the Hamilton Anxiety Rating Scale (HAM-A). Results: Among 148 randomised participants, 70 were assigned to the VR-CBT group and 78 to the control group. The 1-week VR-CBT intervention plus standard mental health support significantly reduced the anxiety symptoms compared with standard mental health support alone in terms of HAM-A scores at both post intervention (Cohen's d=-1.27 (95% confidence interval (CI): -1.64 to -0.90, p<0.001) and 3-month follow-up (Cohen's d=-0.37 (95% CI: -0.72 to -0.01, p=0.024). Of the 70 participants who received VR-CBT, 62 (88.6%) completed the entire intervention. Cybersickness was the main reported adverse event (n=5). Conclusions: Our results indicate that VR-CBT can significantly reduce post-AMI anxiety at the acute stage of the illness; the improvement was maintained at the 3-month follow-up. Trial registration number: The trial was registered at www.chictr.org.cn with the identifier: ChiCTR2200066435.

Effects of different sizes of ambient particulate matter and household fuel use on physical function: National cohort study in China.

BACKGROUND: Impact of outdoor and household air pollution on physical function remains unelucidated. This study examined the influence of various ambient particulate sizes (PM1, PM2.5, and PM10) and household fuel usage on physical function. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) spanning 2011 and 2015 were utilized. The physical functional score was computed by summing scores from four tests: grip strength, gait speed, chair stand test, and balance. Multivariate linear and linear mixed-effects models were used to explore the separate and combined effects of PM1, PM2.5, PM10 and household fuel use on physical function in the cross-sectional and longitudinal analyses, respectively, and to further observe the effects of fuel cleanup on physical function in the context of air pollution exposure. RESULTS: Both cross-sectional and longitudinal analyses revealed negative correlations between PM1 (ß = -0.044; 95% CI: -0.084, -0.004), PM2.5 (ß = -0.024; 95% CI: -0.046, -0.001), PM10 (ß = -0.041; 95% CI: -0.054, -0.029), and physical function, with a more pronounced impact observed for fine particulate matter (PM1). Cleaner fuel use was associated with enhanced physical function compared to solid fuels (ß = 0.143; 95% CI: 0.070, 0.216). The presence of air pollutants and use of solid fuels had a negative impact on physical function, while cleaner fuel usage mitigated the adverse effects of air pollutants, particularly in areas with high exposure. CONCLUSION: This study underscores the singular and combined detrimental effects of air pollutants and solid fuel usage on physical function. Addressing fine particulate matter, specifically PM1, and prioritizing efforts to improve household fuel cleanliness in regions with elevated air pollution levels are crucial for preventing physical disability.

Efficient Sequential Detection of Two Antibiotics Using a Fiber-Optic Surface Plasmon Resonance Sensor.

Antibiotic residues have become a worldwide public safety issue. It is vital to detect multiple antibiotics simultaneously using sensors. A new and efficient method is proposed for the combined detection of two antibiotics (enrofloxacin (Enro) and ciprofloxacin (Cip)) in milk using surface plasmon resonance (SPR) sensors. Based on the principle of immunosuppression, two antibiotic antigens (for Enro and Cip) were immobilized on an optical fiber surface with conjugates of bovine serum albumin using dopamine (DA) polymerization. Each single antigen was bound to its corresponding antibody to derive standard curves for Enro and Cip. The fiber-optic sensor's sensitivity was 2900 nm/RIU. Detection limits were calculated to be 1.20 ng/mL for Enro and 0.81 ng/mL for Cip. The actual system's recovery rate was obtained by testing Enro and Cip in milk samples; enrofloxacin's and ciprofloxacin's mean recoveries from the milk samples were 96.46-120.46% and 96.74-126.9%, respectively. In addition, several different regeneration solutions were tested to analyze the two target analytes' regeneration ability; NaOH and Gly-HCl solutions were found to have the best regeneration ability.

Plastic footprint deteriorates dryland carbon footprint across soil-plant-atmosphere continuum.

Plastic fragments are widely found in the soil profile of terrestrial ecosystems, forming plastic footprint and posing increasing threat to soil functionality and carbon (C) footprint. It is unclear how plastic footprint affects C cycling, and in particularly permanent C sequestration. Integrated field observations (including 13C labelling) were made using polyethylene and polylactic acid plastic fragments (low-, medium- and high-concentrations as intensifying footprint) landfilling in soil, to track C flow along soil-plant-atmosphere continuum (SPAC). The result indicated that increased plastic fragments substantially reduced photosynthetic C assimilation (p < 0.05), regardless of fragment degradability. Besides reducing C sink strength, relative intensity of C emission increased significantly, displaying elevated C source. Moreover, root C fixation declined significantly from 21.95 to 19.2 mg m-2, and simultaneously root length density, root weight density, specific root length and root diameter and surface area were clearly reduced. Similar trends were observed in the two types of plastic fragments (p > 0.05). Particularly, soil aggregate stability was significantly lowered as affected by plastic fragments, which accelerated the decomposition rate of newly sequestered C (p < 0.05). More importantly, net C rhizodeposition declined averagely from 39.77 to 29.41 mg m-2, which directly led to significant decline of permanent C sequestration in soil. Therefore, increasing plastic footprint considerably worsened C footprint regardless of polythene and biodegradable fragments. The findings unveiled the serious effects of plastic residues on permanent C sequestration across SPAC, implying that current C assessment methods clearly overlook plastic footprint and their global impact effects.

Association of lipid-modifying therapy with risk of obstructive sleep apnea: A drug-target mendelian randomization study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered to be an important contributor of dyslipidemia. However, there lacks observational studies focusing on the potential effect of lipid management on OSA risk. Thus, we aimed to investigate the genetic association of lipid-modifying therapy with risk of OSA. METHODS: A drug-target mendelian randomization (MR) study using both cis-variants and cis-expression quantitative trait loci (eQTLs) of lipid-modifying drug targets was performed. The MR analyses used summary-level data of genome wide association studies (GWAS). Primary MR analysis was conducted using inverse-variance-weighted (IVW) method. Sensitivity analysis was performed using weighted median (WM) and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods. RESULTS: Genetically proxied low-density lipoprotein cholesterol (LDL-C)-lowering effect of cholesteryl ester transfer protein (CETP) was associated with reduced risk of OSA (odds ratio [OR] =0.75, 95% confidence interval [CI]: 0.60-0.94, false discovery rate [FDR] q value = 0.046). A significant MR association with risk of OSA was observed for CETP expression in subcutaneous adipose tissue (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049), lung (OR = 0.94, 95%CI: 0.89-1.00, FDR q value = 0.049) and small intestine (OR = 0.96, 95%CI: 0.93-1.00, FDR q value = 0.049). No significant effects of high-density lipoprotein cholesterol (HDL-C)-raising effect of CETP inhibition, LDL-C-lowering and triglycerides-lowering effect of other drug targets on OSA risk were observed. CONCLUSIONS: The present study presented genetic evidence supporting the association of LDL-C-lowering therapy by CETP inhibition with reduced risk of OSA. These findings provided novel insights into the role of lipid management in patients with OSA and encouraged further clinical validations and mechanistic investigations.

Simultaneous Visualization and Depletion of Peroxynitrite by a Simple Aggregation-Induced Emission Nanoprobe for Preventing Breast Cancer Metastasis after Surgery.

Inflammation has been confirmed to be closely related to the development of tumors, while peroxynitrite (ONOO-) is one of the most powerful oxidative pro-inflammatory factors. Although ONOO- can kill bacteria through oxidation, it will activate matrix metalloproteinases (MMPs), accelerate the degradation of the extracellular matrix (ECM), and subsequently lead to the activation and release of other tumor promotion factors existing in the ECM, promoting tumor metastasis and invasion. Herein, we report a simple aggregation-induced emission (AIE) nanoprobe (NP), TPE-4NMB, that can simultaneously visualize and deplete ONOO-. The probe can light up the endogenous and exogenous ONOO- in cells and selectively inhibit the proliferation and migration of 4T1 cells by inducing an intracellular redox homeostasis imbalance through ONOO- depletion. After being modified with DSPE-PEG2000, the TPE-4NMB NPs can be used to image ONOO- induced by various models in vivo; especially, it can monitor the dynamic changes of ONOO- level in the residual tumor after surgery, which can provide evidence for clarifying the association between surgery, ONOO-, and cancer metastasis. Excitingly, inhibited tumor volume growth and decreased counts of lung metastases were observed in the TPE-4NMB NPs group, which can be attributed to the downregulated expression of MMP-9 and transforming growth factor-ß (TGF-ß), increased cell apoptosis, and inhibited epithelial-mesenchymal transition (EMT) mediated by ONOO-. The results will provide new evidence for clarifying the relationship between surgery, ONOO-, and tumor metastasis and serve as a new intervention strategy for preventing tumor metastasis after tumor resection.

Carbopol 940-based hydrogels loading synergistic combination of quercetin and luteolin from the herb Euphorbia humifusa to promote Staphylococcus aureus infected wound healing.

With the increasing prevalence of Staphylococcus aureus infections, rapid emergence of drug resistance and the slow healing of infected wounds, developing an efficient antibiotic-free multifunctional wound dressing for inhibiting S. aureus and simultaneously facilitating wound healing have become a huge challenge. Due to their excellent biocompatibility and biodegradability, some carbopol hydrogels based on plant extracts or purified compounds have already been applied in wound healing treatment. In China, Euphorbia humifusa Willd. (EuH) has been traditionally used as a medicine and food homologous medicine for the treatment of furuncles and carbuncles mainly caused by S. aureus infection. In an earlier study, EuH-originated flavonoids quercetin (QU) and luteolin (LU) could serve as a potential source for anti-S. aureus drug discovery when used in synergy. However, the in vivo effects of QU and LU on S. aureus-infected wound healing are still unknown. In this study, we found a series of Carbopol 940-based hydrogels loading QU and LU in combination could disinfect S. aureus and also could promote wound healing. In the full-thickness skin defect mouse model infected with S. aureus, the wound contraction ratio, bacterial burden, skin hyperplasia and inflammation score, as well as collagen deposition and blood vessels were then investigated. The results indicate that the optimized QL2 [QU (32 µg mL-1)-LU (8 µg mL-1)] hydrogel with biocompatibility significantly promoted S. aureus-infected wound healing through anti-infection, anti-inflammation, collagen deposition, and angiogenesis, revealing it as a promising alternative for infected wound repair.

Construction of an effective method combining in situ capping with electric field-enhanced biodegradation for treating PAH-contaminated soil at abandoned coking sites.

The simultaneous application of in situ capping and electro-enhanced biodegradation may be a suitable method for ensuring the feasibility and safety of reusing abandoned coking sites. However, the capping layer type and applied electric field pattern may affect the efficiency of sequestering and removing pollutants. This study investigated changes in electric current, soil moisture content and pH, polycyclic aromatic hydrocarbon (PAH) concentration, bacterial number, and microbial community structure and metabolic function during soil remediation at abandoned coking plant sites under different applied electric field patterns and barrier types. The results indicated that polarity-reversal electric field was more conducive to maintaining electric current, soil properties, resulting in higher microbial number, community diversity, and functional gene abundance. At 21d, the mean PAH concentrations in contaminated soil, the capping layer's clean soil and barrier were 78.79, 7.56, and 1.57 mg kg-1 lower than those with a unidirectional electric field, respectively. The mean degradation rate of PAHs in the bio-barrier was 10.12 % higher than that in the C-Fe barrier. In the experiment combining a polarity-reversal electric field and a bio-barrier, the mean PAH concentrations in contaminated soil and the capping layer were 706.68 and 27.15 mg kg-1 lower than those in other experiments, respectively, and no PAHs were detected in the clean soil, demonstrating that the combination of the polarity-reversal electric field and the bio-barrier was effective in treating soil at abandoned coking plant sites. The established method of combining in situ capping with electro-enhanced biodegradation will provide technical support for the treatment and reuse of heavily PAH-contaminated soil at abandoned coking plant sites.

Growth of Scenedesmus obliquus in anaerobically digested swine wastewater from different cleaning processes for pollutants removal and biomass production.

Anaerobically digested swine wastewater (ASW) purification by microalgae provides a promising strategy for nutrients recovery, biomass production and CO2 capture. However, the characteristics of ASW from different cleaning processes vary greatly. At present, the cultivation of microalgae in ASW from different manure cleaning processes is rarely investigated and compared. That may bring uncertainty for microalgae growth using different ASW in large-scale application. Thus, the ASW from three cleaning processes were tested for cultivating microalgae, including manure dry collection (I), water flushing (II) and water submerging processes (III). The characteristics of ASW from three manure cleaning processes varied greatly such as nutrient and heavy metals levels. High concentration of ammonia and copper in ASW significantly inhibited microalgae growth. Fortunately, the supply of high CO2 (10%) effectively alleviated negative influences, ensuring microalgal growth at low dilution ratio. The characteristics of three ASW resulted in significant differences in microalgae growth and biomass components. The maximal biomass production in optimal diluted ASW-I, II and III reached 1.46 g L-1, 2.19 g L-1 and 2.47 g L-1, respectively. The removal of organic compounds, ammonia and phosphorus by optimal microalgae growth in diluted ASW-I, II and III was 50.6%/94.2%/64.7%, 63.7%/82.3%/57.6% and 83.2%/91.7%/59.7%, respectively. The culture in diluted ASW-I, II and III obtained the highest lipids production of 12.1 mg L-1·d-1, 16.5 mg L-1·d-1 and 19.4 mg L-1·d-1, respectively. The analysis of lipids compositions revealed that the proportion of saturated fatty acids accounted for 36.4%, 32.4% and 27.9 % in optimal diluted ASW-I, II and III, as ideal raw materials for biodiesel production.

Platanosides from Platanus × acerifolia: New molecules, SAR, and target validation of a strong lead for drug-resistant bacterial infections and the associated sepsis.

Three undescribed (1-3) and nine known (4-12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 µg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 µg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 µM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead.

Irritable bowel syndrome in children: the placebo response rate and influencing factors a meta-analysis.

BACKGROUND: Irritable bowel syndrome is common in children and exhibits a high placebo response. This study was to explore the placebo response rate and its influencing factors in children with irritable bowel syndrome. METHODS: A systematic search was performed on Pubmed, Embase, MEDLINE, Cochrane Library, CNKI, Wanfang, and CBM from database inception to March 2022. Randomized controlled trials of irritable bowel syndrome in children were included in the study. The primary outcome was the placebo response rate of improvement. RESULTS: Thirteen studies were included, with 445 patients in the placebo group. The rate of improvement and abdominal pain disappearance were 28.2% (95% CI, 16.6-39.9%) and 5% (95% CI, 0-18.4%). The placebo response based on the abdominal pain score was 0.675 (95% CI, 0.203-1.147). The mode of administration (P < 0.01), dosing schedule (P < 0.01), and clinical outcome assessor (P = 0.04) have a significant impact on the magnitude of placebo effect. CONCLUSIONS: The placebo response rate for pediatric irritable bowel syndrome was 28.2%. In clinical trials, reducing dosing frequency, selecting appropriate dosage forms, and using patient-reported outcomes can help mitigate the placebo effect. IMPACT: This is the first meta-analysis to assess the placebo response rates for improvement and disappearance in children with IBS. The finding suggested that the mode of administration, dosing schedule, and clinical outcome assessor could potentially influence the magnitude of the placebo effect in children with IBS. This study would provide a basis for estimating sample size in clinical trial design with a placebo control.

Toward a solid microneedle patch for rapid and enhanced local analgesic action.

Analgesic creams find widespread application as adjuncts for localized anesthesia prior to surgical procedures. Nevertheless, the onset of analgesic action is protracted due to the skin barrier's inherent characteristics, which necessitates prolonged intervals of patient and clinician waiting, consequently impinging upon patient compliance and clinician workflow efficiency. In this work, a biodegradable microneedles (MNs) patch was introduced to enhance the intradermal administration of lidocaine cream to achieve rapid analgesia through a minimally invasive and conveniently accessible modality. The polylactic acid (PLA) MNs were mass-produced using a simple hot-pressing method and served the purpose of creating microchannels across the skin's surface for rapid absorption of lidocaine cream. Optical and electron microscopes were applied to meticulously scrutinize the morphology of the fabricated MNs, and the comprehensive penetration tests involving dynamometer tests, evaluation on porcine cadaver skin, artificial film, optical coherence tomography (OCT), transepidermal water loss, and analysis on rats' skins, demonstrated the robust mechanical strength of PLA MNs for successful intradermal penetration. The behavioral pain sensitivity tests on living rats using Von Frey hair filaments revealed that the MN-assisted lidocaine treatment expeditiously accelerated the onset of action from 40 to 10 min and substantially enhanced the efficacy of localized anesthesia. Furthermore, different treatment protocols encompassing the sequence of drug application relative to MN treatment, MN dimensions, and the frequency of MN insertions exhibited noteworthy influence on the resultant local anesthesia efficacy. Together, these results demonstrated that the lidocaine cream followed by diverse PLA MN treatments would be a promising strategy for rapid clinical local anesthesia with wide-ranging applications.

Terricoxanthones A-E, unprecedented dihydropyran-containing dimeric xanthones from the endophytic fungus Neurospora terricola HDF-Br-2 associated with the vulnerable conifer Pseudotsuga gaussenii.

An investigation on the secondary metabolites from a rice culture broth of the endophytic fungus Neurospora terricola HDF-Br-2 derived from the vulnerable conifer Pseudotsuga gaussenii led to the isolation and characterization of 34 structurally diverse polyketides (1-34). Seven of them are previously undescribed, including five unprecedented dihydropyran-containing (terricoxanthones A-E, 1-5, resp.) and one rare tetrahydrofuran-containing (terricoxanthone F, 6) dimeric xanthones. The structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction analyses. Terricoxanthones each were obtained as a racemic mixture. Their plausible biosynthetic relationships were briefly proposed. Compounds 6, aspergillusone A (8), and alatinone (27) displayed considerable inhibition against Candida albicans with MIC values of 8-16 µg/mL. 4-Hydroxyvertixanthone (12) and 27 exhibited significant inhibitory activities against Staphylococcus aureus, with MIC values of 4-8 µg/mL. Furthermore, compounds 8 and 27 could disrupt biofilm of S. aureus and C. albicans at 128 µg/mL. The findings not only extend the skeletons of xanthone dimers and contribute to the diversity of metabolites of endophytes associated with the endangered Chinese conifer P. gaussenii, but could further reveal the important role of protecting plant species diversity in support of chemical diversity and potential sources of new therapeutics.

Liposomes modified with a multivalent glutamic hexapeptide: A novel and effective way to promote bone targeting.

It is well known that bone-related diseases are difficult to treat due to the relatively low blood flow. Therefore, targeting the delivery of drugs to bone may not only improve the therapeutic effect but also reduce the dose. To prepare liposomes, a series of novel multivalent glutamic hexapeptide derivatives were designed and synthesized as liposome ligands, which can effectively deliver paclitaxel (PTX) to bone. The liposomes were prepared and their encapsulation efficiency, particle size, stability, zeta potential, hemolysis, and release behavior were characterized. The results indicated that the coated liposomes, PTX-Glu61 -Lip, PTX-Glu62 -Lip, PTX-Glu63 -Lip, and PTX-Glu65 -Lip, showed remarkable bone-targeting activity. Compared with the other coated liposomes, PTX-Glu65 -Lip showed prominent targeting ability and anti-bone metastasis activity on the basis of in vitro and in vivo evaluations. Our study may contribute to the field of design of bone-targeting drugs.