Effect of Alloying Elements on the High-Temperature Yielding Behavior of Multicomponent γ'-L12 Alloys.

The exceptional mechanical properties of Ni-based high entropy alloys are due to the presence of ordered L12 (γ') precipitates embedded within a disordered matrix phase. While the strengthening contribution of the γ' phase is generally accepted, there is no consensus on the precise contribution of the individual strengthening mechanisms to the overall strength. In addition, changes in alloy composition influence several different mechanisms, making the assessment of alloying conditions complex. Multicomponent L12-ordered single-phase alloys were systematically developed with the aid of CALPHAD thermodynamic calculations. The alloying elements Co, Cr, Ti, and Nb were chosen to complexify the Ni3Al structure. The existence of the γ' single phase was validated by microstructure characterization and phase identification. A high-temperature compression test from 500 °C to 1000 °C revealed a positive temperature dependence of strength before reaching the peak strength in the studied alloys NiCoCrAl, NiCoCrAlTi, and NiCoCrAlNb. Ti and Nb alloying addition significantly enhanced the high-temperature yield strengths before the peak temperature. The yield strength was modeled by summing the individual effects of solid solution strengthening, grain boundary strengthening, order strengthening, and cross-slip-induced strengthening. Cross-slip-induced strengthening was shown to be the key contributor to the high-temperature strength enhancement.

The diagnostic performance of GeneXpert MTB/RIF in tuberculosis meningitis: A multicentre accuracy study.

OBJECTIVES: To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. METHODS: An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. RESULTS: The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). CONCLUSIONS: The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose.

Hypoxia-Induced Myocardial Hypertrophy Companies with Apoptosis Enhancement and p38-MAPK Pathway Activation.

Li, Xiaoxu, Zhijun Pu, Gang Xu, Yidong Yang, Yu Cui, Xiaoying Zhou, Chenyuan Wang, Zhifeng Zhong, Simin Zhou, Jun Yin, Fabo Shan, Chengzhong Yang, Li Jiao, Dewei Chen, and Jian Huang. Hypoxia-induced myocardial hypertrophy companies with apoptosis enhancement and p38-MAPK pathway activation. High Alt Med Biol. 00:00-00, 2024. Background: Right ventricular function and remodeling are closely associated with symptom severity and patient survival in hypoxic pulmonary hypertension. However, the detailed molecular mechanisms underlying hypoxia-induced myocardial hypertrophy remain unclear. Methods: In Sprague-Dawley rats, hemodynamics were assessed under both normoxia and hypobaric hypoxia at intervals of 7 (H7), 14 (H14), and 28 (H28) days. Morphological changes in myocardial tissue were examined using hematoxylin and eosin (HE) staining, while myocardial hypertrophy was evaluated with wheat germ agglutinin (WGA) staining. Apoptosis was determined through TUNEL assays. To further understand the mechanism of myocardial hypertrophy, RNA sequencing was conducted, with findings validated via Western blot analysis. Results: The study demonstrated increased hypoxic pulmonary hypertension and improved right ventricular diastolic and systolic function in the rat models. Significant elevations in pulmonary arterial systolic pressure (PASP), mean pulmonary arterial pressure (mPAP), right ventricular mean pressure (RVMP), and the absolute value of +dp/dtmax were observed in the H14 and H28 groups compared with controls. In addition, right ventricular systolic pressure (RVSP), -dp/dtmax, and the mean dp/dt during isovolumetric relaxation period were notably higher in the H28 group. Heart rate increased in the H14 group, whereas the time constant of right ventricular isovolumic relaxation (tau) was reduced in both H14 and H28 groups. Both the right heart hypertrophy index and the heart weight/body weight ratio (HW/BW) were elevated in the H14 and H28 groups. Myocardial cell cross-sectional area also increased, as shown by HE and WGA staining. Western blot results revealed upregulated HIF-1α levels and enhanced HIF-2α expression in the H7 group. In addition, phosphorylation of p38 and c-fos was augmented in the H28 group. The H28 group showed elevated levels of Cytochrome C (Cyto C), whereas the H14 and H28 groups exhibited increased levels of Cleaved Caspase-3 and the Bax/Bcl-2 ratio. TUNEL analysis revealed a rise in apoptosis with the extension of hypoxia duration in the right ventricle. Conclusions: The study established a link between apoptosis and p38-MAPK pathway activation in hypoxia-induced myocardial hypertrophy, suggesting their significant roles in this pathological process.

A bibliometric analysis of gastric cancer liver metastases: advances in mechanisms of occurrence and treatment options.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, and its poor prognosis is predominantly attributed to distant metastasis. The liver is the primary site of GC metastasis. However, there is no universally approved treatment regimen for liver metastasis in GC. The aim of this article is to review the current research status and trends of liver metastasis of GC worldwide. METHODS: The authors utilized the Web of Science Core Collection database to identify articles on liver metastasis from GC published between 2000 and 2022. The authors used bibliometric methods to analyze authors, institutions, countries, journals, and references through CiteSpace and VOSviewer. A total of 1003 articles were included in this study. RESULTS: Japan published the most articles in the field, followed by China. Nagoya University is the leading institution in the field of liver metastases in GC. Yasuhiro Kodera from Japan has made significant achievements in this area. The authors identified GC to be the most influential journal in this field. Using cluster analysis, the keywords were divided into four major clusters:(1) the molecular mechanism of GC liver metastasis, (2) prognosis, (3) liver resection, and (4) chemotherapy. CONCLUSION: Our study systematically summarizes the results of GC liver metastasis research from 2000 to 2022 and describes and predicts research hotspots and trends on a global scale. Research on the molecular mechanisms of GC liver metastasis will become a hot topic in the future, and the expansion of the surgical treatment scope and the advancement of translational therapy will benefit more patients.

Enhancing Deep-Seated Melanoma Therapy through Wearable Self-Powered Microneedle Patch.

Effective treatment of deep-seated tumors relies on enhanced drug penetration in transdermal drug delivery systems. While microneedles (MNs) and iontophoresis techniques have shown improved transdermal drug delivery efficiency, challenges such as skin elasticity, high electrical resistance of the stratum corneum, and external power supply requirements hinder their efficacy in treating deep-seated tumors. In this study, a wearable, self-powered MN patch that integrates a flexible triboelectric nanogenerator (F-TENG) is presented, aimed at advancing deep-seated tumor therapy. MNs are composed of water-soluble materials mixed with negatively charged pH-responsive nanoparticles (NPs) loaded with therapeutic drugs. The F-TENG harnesses personal mechanical movements generate electrical energy. Leveraging the advantages of both MNs and F-TENG, therapeutic NPs can penetrate deep skin locations upon MN patch insertion, releasing drugs rapidly in acidic tumor tissues. Owing to these features, a single administration of the integrated MN-patch in a mouse model with deep-seated melanoma exhibits superior therapeutic efficacy in inhibiting deep-located tumor compared to using the MN-patch alone, indicating promising potential for treating tumors at deep sites.

Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance.

The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.

A self-monitoring microneedle patch for light-controlled synergistic treatment of melanoma.

Melanoma is the most aggressive and malignant form of skin cancer. Current melanoma treatment methods generally suffer from frequent drug administration as well as difficulty in direct monitoring of drug release. Here, a self-monitoring microneedle (MN)-based drug delivery system, which integrates a dissolving MN patch with aggregation-induced emission (AIE)-active PATC microparticles, is designed to achieve light-controlled pulsatile chemo-photothermal synergistic therapy of melanoma. The PATC polymeric particles, termed D/I@PATC, encapsulate both of chemotherapeutic drug doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon light illumination, PATC gradually dissociates into smaller particles, causing the release of encapsulated DOX and subsequent fluorescence intensity change of PATC particles, thereby not only enabling direct observation of the drug release process under light stimuli, but also facilitating verification of drug release by fluorescence recovery after light trigger. Moreover, encapsulation of ICG in PATC particles displays significant improvement of its photothermal stability both in vitro and in vivo. In a tumor-bearing mouse, the application of one D/I@PATC MN patch combining with two cycles of light irradiation showed excellent controllable chemo-photothermal efficacy and exhibited ∼97% melanoma inhibition rate without inducing any evident systemic toxicity, suggesting a great potential for skin cancer treatment in clinics.

Multifunctional MOF-Based Microneedle Patch With Synergistic Chemo-Photodynamic Antibacterial Effect and Sustained Release of Growth Factor for Chronic Wound Healing.

Chronic wound healing is a major challenge in biomedicine. Conventional therapies are usually associated with poor drug permeability, low bioavailability, risk of antimicrobial resistance, and require frequent administration. Therefore, a novel formulation with reduced antibiotic dosage, improved drug delivery efficiency, and low application frequency is of remarkable interest for chronic wound healing. Herein, a multifunctional microneedle (MN) patch is presented to achieve rapid wound healing via efficient chemo-photodynamic antibacterial effect and sustained release of growth factors at the wound bed. When the MN patch pierces the skin, MN tips carrying both low dosage of antibiotics and bioactive small molecule-encapsulated metal-organic frameworks (MOFs) rapidly dissolve and subsequently deliver the payloads to the wound. Upon light irradiation, MOF-based nanoparticles robustly convert O2 into 1 O2 , which acts synergistically with chemotherapy to remove pathogenic bacteria from the wound, exhibiting excellent chemo-photodynamic antibacterial performance with a tenfold reduction in the required antibiotic amount. The nanoparticles can achieve a continuous release of growth factors in the wound tissue, promoting the formation of epithelial tissue and neovascularization, thereby further accelerating chronic wound healing. Collectively, the designed multifunctional MOF-based MN patches offer a simple, safe, and effective alternative for chronic wound management.

Dissolving Microneedle Patch Integrated with Microspheres for Long-Acting Hair Regrowth Therapy.

Androgenetic alopecia (AGA) is the most common type of progressive hair loss in both men and women that severely reduces life quality and affects patients' self-esteem. Due to the shortcomings of traditional therapeutic formulations (e.g., topical minoxidil and oral finasteride), such as low bioavailability, frequent dosing, and significant side effects, there is an urgent need to develop a safe and effective strategy for AGA treatment. Here, we report a water-soluble microneedle (MN) patch integrated with biodegradable minoxidil (MXD)-loaded microspheres for long-acting AGA treatment with reduced administration frequency and improved patient compliance. When the patch pierces the skin, the MNs rapidly dissolve and deliver MXD-encapsulated polylactic-co-glycolic acid (PLGA) microspheres into the skin, which, subsequently act as drug reservoirs for the sustained release of the therapeutics for over 2 weeks. Additionally, the application of the MN patch provided a mechanical stimulation on mouse skin, which was also helpful for hair regrowth. Compared with the topical MXD solutions that have been commercialized on the market and require daily application, the long-acting MN patch contains a much lower drug amount and shows a similar or superior hair regeneration effect in AGA mice while only requiring monthly or weekly administration. These encouraging results suggest a simple, safe, and effective strategy for long-acting hair regeneration in clinics.

Prevalence, antimicrobial susceptibility, and antibiotic resistance gene transfer of Bacillus strains isolated from pasteurized milk.

Pasteurization is carried out in dairy industries to kill harmful bacteria present in raw milk. However, endospore-forming bacteria, such as Bacillus, cannot be completely eliminated by pasteurization. In this study, a total of 114 Bacillus strains were isolated from 133 pasteurized milk samples. Antibiotic susceptibility tests showed that the percentage of Bacillus with intrinsic resistance to ampicillin and penicillin were 80 and 86%, respectively. Meanwhile, some Bacillus isolates had acquired resistance, including trimethoprim-sulfamethoxazole resistance (10 isolates), clindamycin resistance (8 isolates), erythromycin resistance (2 isolates), and tetracycline resistance (1 isolate). To further locate these acquired resistance genes, the plasmids were investigated in these 16 Bacillus strains. The plasmid profile indicated that Bacillus cereus BA008, BA117, and BA119 harbored plasmids, respectively. Subsequently, the Illumina Novaseq PE150 was applied for the genomic and plasmid DNA sequencing. Notably, the gene tetL encoding tetracycline efflux protein was found to be located on plasmid pBC46-TL of B. cereus BA117. In vitro conjugative transfer indicated that pBC46-TL can be transferred into Bacillus invictae BA142, Bacillus safensis BA143, and Bacillus licheniformis BA130. The frequencies were of 1.5 × 10-7 to 1.7 × 10-5 transconjugants per donor cells. Therefore, Bacillus strains with acquired antibiotic resistance may represent a potential risk for the spread of antibiotic resistance between Bacillus and other clinical pathogens via horizontal gene transfer.

Impact Assessment of the Ms7.0 Earthquake on Jiuzhaigou Valley from the Perspective of Vegetation Net Primary Productivity.

In order to assess the impact of the Ms7.0 Jiuzhaigou earthquake that occurred on 8 August 2017 on vegetation, the Carnegie-Ames-Stanford Approach (CASA) model was adopted to estimate the vegetation net primary productivity (NPP) of Jiuzhaigou Valley, one of the World Heritage Sites, in July, August and September from 2015 to 2019. Then the characteristics of the impact of different earthquake-induced geohazards on vegetation were discussed, and a vulnerability-resilience assessment system concerning the seismic intensity was proposed. The results show that the NPPmax and NPPmean values in Jiuzhaigou Valley first decreased and then increased and were 151.5-261.9 gC/m2 and 54.6-116.3 gC/m2, respectively. The NPP value of more than 70% area was 90-150 gC/m2 in July. In August, the NPPmean values decreased, and the areas with lower values became larger; the NPPmean values of most areas affected by geohazards were 60-150 gC/m2. During the earthquake, the NPPmean values of areas hit by geohazards sharply declined by 27.2% (landslide), 22.4% (debris flow) and 15.7% (collapse) compared with those in the same month in 2016. Vegetation in debris flow zones showed a stronger recovery, with a maximum NPP value increase of about 23.0% in September 2017. The vegetation gradually recovered after the earthquake, as indicated by the uptrend of the NPP values in the corresponding period in 2018 and 2019. In general, the reduction magnitude of NPP values decreased year by year in comparison to that in 2015 and 2016, and the decrease slowed down after the earthquake. The vulnerability and resilience index corresponding to the three seismic intensity ranges were 0.470-0.669 and 0.642-0.693, respectively, and those of Jiuzhaigou Valley were 0.473 and 0.671, respectively. The impact coefficient defined to represent the impact of the earthquake on NPP was 0.146-0.213. This paper provides a theoretical reference and guidance for the impact assessment of earthquakes on the ecosystem.

Progresses of animal robots: A historical review and perspectiveness.

Animal robots have remarkable advantages over traditional mechatronic ones in terms of energy supply, self-orientation, and natural concealment and can provide remarkable theoretical and practical values for scientific investigation, community service, military detection and other fields. Given these features, animal robots have become high-profile research objects and have recently attracted extensive attention. Herein, we have defined animal robots, reviewed the main types of animal robots, and discussed the potential developing directions. We have also detailed the mechanisms underlying the regulation of animal robots and introduced key methods for manipulating them. We have further proposed several application prospects for different types of animal robots. Finally, we have presented research directions for their further improvement.

Effects of Fermented Milk Containing Bifidobacterium animalis Subsp. lactis MN-Gup (MN-Gup) and MN-Gup-Based Synbiotics on Obesity Induced by High Fat Diet in Rats.

Given the probiotic effects previously found in Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and its great application potential in dairy products, this study aimed to investigate the effects of fermented milk containing MN-Gup or MN-Gup-based synbiotics on high fat diet (HFD)-induced obesity in rats. Galacto-oligosaccharides (GOS) and xylo-oligosaccharides (XOS) were selected as the tested prebiotics in MN-Gup-based synbiotics due to their promotion of MN-Gup growth in vitro. After nine weeks of HFD feeding, the obese rats were intervened with fermented milk containing MN-Gup (MN-Gup FM) or its synbiotics (MN-Gup + GOS FM, MN-Gup + XOS FM) for eight weeks. The results showed that the interventions could alleviate HFD-induced body weight gain, epididymal fat deposition, adipocyte hypertrophy, dyslipidemia and inflammation, but GOS and XOS did not exhibit significant synergies with MN-Gup on those alleviations. Furthermore, the interventions could regulate the HFD-affected gut microbiota and microbial metabolites, as shown by the increases in short chain fatty acids (SCFAs) and alterations in obesity-related bile acids (BAs), which may play important roles in the mechanism underlying the alleviation of obesity. This study revealed the probiotic effects of MN-Gup on alleviating obesity and provided the basis for MN-Gup applications in the future.

Derivation and Verification of the Relationship between Ablation Index and Baseline Impedance.

OBJECTIVE: To explore the quantitative adjustment of ablation index (AI) under different baseline impedance to achieve similar lesion dimensions. METHODS: (1) Keeping the AIs relatively constant, the lesion dimensions in different baseline impedances were studied. (2) According to Joule's law, Q = I 2RT, keeping the current (I) unchanged, the powers corresponding to different baseline impedances can be obtained. Under different baseline impedances and corresponding powers, the swine hearts were ablated for 30 s in simulated human circumstances. The baseline impedances, the lesion dimensions, and AIs were recorded. And the derivation of empirical formula was achieved according to the AIs and baseline impedance values in similar lesions dimension. (3) Basic AI and baseline impedance (AI0/R 0) were set as 400/120 Ω in the common AI groups and 550/120 Ω in the high AI groups, AI values in different baseline impedances were calculated using the empirical formula, and the corresponding lesion dimensions were measured to verify this formula. RESULTS: (1) Higher baseline impedances were related to smaller lesion dimensions at similar AIs. (2) The lesion dimensions were roughly the same after modulating the baseline impedance and power to keep the electric current relatively constant. The relationship between AI and R fitted with experimental data is AI = 1.9933R + 203.61 (r = 0.9649), and the formula derived is ΔAI = (AI0 - 203)/R 0 × ΔR. (3) Under the guidance of the empirical formula, there was no significant difference in lesion dimensions between the standard group and the formula guiding groups when AI0 = 400, but there was a shrinking tendence when AI > 700. CONCLUSION: The lesion depths are negatively correlated with baseline impedance at a certain AI. The relationship between baseline impedance and AI is "ΔAI = (AI0 - 203)/R 0 × ΔR". It is verified that when the AI is not too high, the empirical formula can be used to guide the quantitative adjustment of AIs at different baseline impedance, and the lesion depths achieved are roughly the same.

Erratum: Acidic Microenvironment Up-Regulates Exosomal miR-21 and miR-10b in Early-Stage Hepatocellular Carcinoma to Promote Cancer Cell Proliferation and Metastasis: Erratum.

[This corrects the article DOI: 10.7150/thno.30958.].

Defect-engineered porphyrinic metal-organic framework nanoparticles for targeted multimodal cancer phototheranostics.

Defect-engineered porphyrinic MOF nanoparticles were fabricated with an in situ one-pot protocol using cypate as the co-ligand and modulator. This multifunctional nanoplatform integrated the photothermal and multimodal imaging properties of cypate with the photodynamic effects of porphyrins, thus achieving targeted multimodal cancer phototheranostics after folic acid modification.

Maternal Fucosyltransferase 2 Status Associates with the Profiles of Human Milk Oligosaccharides and the Fecal Microbiota Composition of Breastfed Infants.

Human milk oligosaccharides (HMOs) play key roles in shaping infant fecal microbiota, and HMOs profiles have been reported to vary according to the mother's glycosyltransferase phenotype. In this study, the profiles of HMOs in human milk from secretor or non-secretor mothers collected at 2 months postpartum were analyzed by liquid chromatography quadrupole time-of-flight tandem mass spectrometry. 16S rRNA sequencing was used to characterize the fecal microbiota of breastfed infants. The amount of total and fucosylated HMOs were higher in secretor than non-secretor mothers, while Bifidobacterium genus were highly enriched in infants fed by non-secretor mothers. Associations between HMOs and infant fecal microbiota showed that the relative abundance of Bifidobacterium-OTU158 was positively associated with 2'-fucosyllactose and 3-fucosyllactose, and Bifidobacterium-OTU90 was negatively associated with lacto-N-difucohexaose. The present study provides the HMO profiles from Chinese mothers and their associations with infant fecal microbiota composition, suggesting that HMO compositions are associated with different Bifidobacterium strains in species-specific manner.