Transition from Kwon [4+2]- to [3+2]-cycloaddition enabled by AgF-assisted phosphine catalysis.

Phosphine catalysis generally relies on the potential of carbanion-phosphonium zwitterions that are generated via nucleophilic addition of phosphine catalyst to electrophilic reactants. Consequently, structural modification of zwitterions using distinct electrophilic reactants has emerged as a prominent strategy to enhance catalysis diversity. Herein, we present an alternative strategy that utilizes AgF additive to expand phosphine catalysis. We find that AgF can readily transform the canonical carbanion-phosphonium zwitterion into silver enolate-fluorophosphorane intermediate, eventually furnishing a P(III)/P(V) catalytic cycle. This strategy has been successfully applied to the phosphine-catalyzed reaction of 2-substituted allenoate and imine, resulting in the transition from Kwon [4 + 2] cycloaddition to [3 + 2] cycloaddition. This [3 + 2] cycloaddition features remarkable diastereoselectivity, high yield, and broad substrate scope. Experimental and computational studies have validated the proposed mechanism. Given the prevalence of carbanion-phosphonium zwitterions in phosphine catalysis, this AgF-assisted strategy is believed to hold significant potential for advancing P(III)/P(V) catalysis.

Land use and spatial contiguity are key driven factors of antibiotic multimedia patterns in the megacity river network.

The widespread spread of antibiotics in the environment poses a growing threat to human health. This study investigated the distribution and fate of antibiotics concerning land use characteristics, hydrological conditions, and spatial contiguity within a megacity river network. Temporally, the average concentrations of twenty antibiotics in water (354 ng/L), suspended particulate matter (SPM) (46 ng/L), and sediment (151 ng/g) during dry season were notably higher than that in the corresponding environment media (water: 127 ng/L, SPM: 2 ng/L, and sediment: 49 ng/g) during the wet season. Moreover, the inter-annual variation of antibiotics in water showed a decreasing trend. Spatially, substantial antibiotic contamination was observed in a human-intensive watershed, particularly in the upstream and central city sections. The macrolides in water were most affected by land use types and hydrological processes. Antibiotic contamination in water exhibited a stronger spatial autocorrelation compared to other media. Nevertheless, the interconnectedness of antibiotic contamination in sediments during the wet season warrants attention, and relevant authorities should enhance environmental monitoring in watersheds with pollution hotspots. Certain antibiotics, such as sulfamethoxazole, enrofloxacin, and florfenicol, were transported via urban rivers to the ocean, potentially posing environmental risks to coastal water quality. Local sources accounted for the predominant portion (>50 %) of most antibiotics in various media. The correlation distances of antibiotics in waters during the wet season could screen ecological risk prioritization in aquatic environments.

The association of the severity of Omicron with menstrual and premenstrual syndrome among reproductive age women in China: a cross-sectional study.

This study aimed to investigate changes in menstruation and the association of the severity of Omicron with menstruation after the nationwide outbreak of COVID-19 in China. A cross-sectional study adopted an electronic questionnaire to conduct an anonymous online survey. The survey targeted women of reproductive age who had been infected with SARS-CoV-2, and were menstruating regularly in the six months prior to the infection, and experienced at least one menstrual cycle after the infection. The 737 included participants were divided into mild and severe groups based on the severity of the infection. Deviations in first menstrual cycle post-infection were reported in 46.4% of participants (mild group 40.1% vs. severe group 55.2%, P<0.05). Menstrual changes were predominantly a late menstrual period (mild group 25.3% vs. severe group 30.4%), a shorter duration of menstrual flow (mild group 10.4% vs. severe group 14.7%), and a decrease in menstrual flow volume (mild group 16% vs. severe group 21.6%). Premenstrual syndrome symptoms in a small number of women were worse compared with pre-infection, especially in the severe group. During the second menstrual period after infection, most participants reported their menstrual characteristics had returned to those of pre-infection (mild group 88% vs. severe group 80.2%, P<0.05). In this investigation, SARS-CoV-2 infection had a substantial effect on women's menstrual characteristics, and the changes were mostly transient. Women with more severe COVID-19 symptoms experienced more significant changes. The potential long-term effects of SARS-CoV-2 on female reproductive health require further observation and research.

Cette étude visait à étudier les changements dans la menstruation et l'association entre la gravité d'Omicron et la menstruation après l'épidémie nationale de COVID-19 en Chine. Une étude transversale a adopté un questionnaire électronique pour mener une enquête anonyme en ligne. L'enquête visait les femmes en âge de procréer qui avaient été infectées par le SRAS-CoV-2, qui avaient leurs règles régulièrement au cours des six mois précédant l'infection et qui ont connu au moins un cycle menstruel après l'infection. Les 737 participants inclus ont été divisés en groupes légers et sévères en fonction de la gravité de l'infection. Des écarts dans le premier cycle menstruel post-infection ont été signalés chez 46,4 % des participantes (groupe léger 40,1 % contre groupe sévère 55,2 %, P <0,05). Les changements menstruels étaient principalement une période menstruelle tardive (groupe léger 25,3 % contre groupe sévère 30,4 %), une durée plus courte du flux menstruel (groupe léger 10,4 % contre groupe sévère 14,7 %) et une diminution du volume du flux menstruel (groupe léger). 16 % contre groupe sévère 21,6 %). Les symptômes du syndrome prémenstruel chez un petit nombre de femmes étaient pires que ceux observés avant l'infection, en particulier dans le groupe sévère. Au cours de la deuxième période menstruelle après l'infection, la plupart des participantes ont déclaré que leurs caractéristiques menstruelles étaient revenues à celles d'avant l'infection (groupe léger 88 % contre groupe sévère 80,2 %, P <0,05). Dans cette enquête, l'infection par le SRAS-CoV-2 a eu un effet substantiel sur les caractéristiques menstruelles des femmes, et les changements ont été pour la plupart transitoires. Les femmes présentant des symptômes plus graves de la COVID-19 ont connu des changements plus importants. Les effets potentiels à long terme du SRAS-CoV-2 sur la santé reproductive des femmes nécessitent des observations et des recherches plus approfondies.

Efficacy and safety of fire needle therapy in treating non-segmental stable vitiligo: A randomized self-controlled clinical trial.

BACKGROUND: Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy. However, rigorous evidence on its efficacy is lacking. OBJECTIVE: We aimed to evaluate the efficacy and safety of fire needle therapy, alone and combined with topical tacrolimus ointment, for non-segmental stable vitiligo. METHODS: In this 6-month randomized self-controlled trial, 35 vitiligo patients were enrolled, providing three similar lesions each. Lesions were randomly allocated to receive fire needle monotherapy, 0.1% tacrolimus ointment monotherapy, or combined fire needle and tacrolimus ointment therapy. The main outcome was change in vitiligo surface area. RESULTS: In total, 29 patients completed the 6-month follow-up. The combination therapy group showed significantly greater reductions in vitiligo surface area compared to monotherapy groups starting at months 4 and 5. By the end of the study, combination therapy resulted in remarkably higher repigmentation responses, with 89.7% of lesions showing at least mild (≥25%) repigmentation and 51.7% showing good (≥50%) repigmentation. This significantly exceeded the outcomes with topical tacrolimus ointment alone, which only achieved 6.9% mild response and 6.9% good response. Fire needle monotherapy also demonstrated steady repigmentation over time, with 69% of lesions attaining a mild response by month 6. Importantly, no major adverse events occurred. CONCLUSION: This study provides promising preliminary evidence supporting the use of fire needle therapy, alone or in combination with topical tacrolimus ointment, for inducing repigmentation in non-segmental stable vitiligo. As a non-pharmacological approach, fire needle therapy warrants further study as an alternative vitiligo treatment.

Bacterial c-di-GMP triggers metamorphosis of mussel larvae through a STING receptor.

Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING (McSTING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.

Association of blood pressure and outcomes differs upon cerebral perfusion post-thrombectomy in patients with acute ischemic stroke.

BACKGROUND: The relationship between post-endovascular thrombectomy (EVT) blood pressure (BP) and outcomes in patients with acute ischemic stroke (AIS) remains contentious. We aimed to explore whether this association differs with different cerebral perfusion statuses post-EVT. METHODS: In a multicenter observational study of patients with AIS with large vessel occlusion who underwent EVT, we enrolled those who accepted CT perfusion (CTP) imaging within 24 hours post-EVT. We recorded post-EVT systolic (SBP) and diastolic BP. Patients were stratified into favorable perfusion and unfavorable perfusion groups based on the hypoperfusion intensity ratio (HIR) on CTP. The primary outcome was good functional outcome (90-day modified Rankin Scale score of ≤3). Secondary outcomes included early neurological deterioration, infarct size growth, and symptomatic intracranial hemorrhage. RESULTS: Of the 415 patients studied (mean age 62 years, 75% male), 233 (56%) achieved good functional outcomes. Logistic regression showed that post-EVT HIR and 24-hour mean SBP were significantly associated with functional outcomes. Among the 326 (79%) patients with favorable perfusion, SBP <140 mmHg was associated with a higher percentage of good functional outcomes compared with SBP ≥140 mmHg (68% vs 52%; aOR 1.70 (95% CI 1.00 to 2.89), P=0.04). However, no significant difference was observed between SBP and functional outcomes in the unfavorable perfusion group. There was also no discernible difference between SBP and secondary outcomes across the different perfusion groups. CONCLUSIONS: In patients with favorable perfusion post-EVT, SBP <140 mmHg was associated with good functional outcomes, which underscores the need for further investigations with larger sample sizes or a more individualized BP management strategy. CLINICAL TRIAL REGISTRATION: ChiCTR1900022154.

Molecular mechanism of endophytic bacteria DX120E regulating polyamine metabolism and promoting plant growth in sugarcane.

Introduction: Sugarcane endophytic nitrogen-fixing bacterium Klebsiella variícola DX120E displayed broad impact on growth, but the exact biological mechanism, especially polyamines (PAs) role, is still meager. Methods: To reveal this relationship, the content of polyamine oxidase (PAO), PAs, reactive oxygen species (ROS)-scavenging antioxidative enzymes, phytohormones, 1-aminocyclopropane-1-carboxylic synthase (ACS), chlorophyll content, and biomass were determined in sugarcane incubated with the DX120E strain. In addition, expression levels of the genes associated with polyamine metabolism were measured by transcriptomic analysis. Results: Genomic analysis of Klebsiella variícola DX120E revealed that 39 genes were involved in polyamine metabolism, transport, and the strain secrete PAs in vitro. Following a 7-day inoculation period, DX120E stimulated an increase in the polyamine oxidase (PAO) enzyme in sugarcane leaves, however, the overall PAs content was reduced. At 15 days, the levels of PAs, ROS-scavenging antioxidative enzymes, and phytohormones showed an upward trend, especially spermidine (Spd), putrescine (Put), catalase (CAT), auxin (IAA), gibberellin (GA), and ACS showed a significant up-regulation. The GO and KEGG enrichment analysis found a total of 73 differentially expressed genes, involving in the cell wall (9), stimulus response (13), peroxidase activity (33), hormone (14) and polyamine metabolism (4). Discussion: This study demonstrated that endophytic nitrogen-fixing bacteria stimulated polyamine metabolism and phytohormones production in sugarcane plant tissues, resulting in enhanced growth. Dual RNA-seq analyses provided insight into the early-stage interaction between sugarcane seedlings and endophytic bacteria at the transcriptional level. It showed how diverse metabolic processes selectively use distinct molecules to complete the cell functions under present circumstances.

Complete genome sequence of Psychrobacter cibarius AOSW16051, a trimeric autotransporter adhesin synthesizing bacterium isolated from the Baltic Sea.

Bacteria of the genus Psychrobacter are widely distributed in the global low-temperature marine environment and have been studied for their effects on the settlement and metamorphosis of marine invertebrates. Psychrobacter cibarius AOSW16051 was isolated from the surface water samples of the Baltic Sea on the edge of the Arctic Ocean. Here, we present the complete genome of strain AOSW16051, which consists of a circular chromosome composed of 3,425,040 nucleotides with 42.98% G + C content and a circular plasmid composed of 5846 nucleotides with 38.66% G + C content. The genes predicted in this strain showed its strong outer membrane system, type VI secretion system and adhesion system. Trimeric autotransporter adhesins (TAAs) has been identified in the genome of P. cibarius AOSW16051, which has a variety of biological functions in interacting with host cells. However, there are no reports on TAAs in marine bacteria and aquatic pathogenic bacteria. By analyzing the genomic data, we can gain valuable insights to enhance our understanding of the physiological characteristics of P. cibarius, as well as the biological functions of TAAs and their role in triggering metamorphosis of invertebrate larvae.

Effect of Yttrium on Ce/Ni-Metakaolin Catalysts for CO2 Methanation.

In recent years, major economies have implemented carbon reduction and carbon neutrality policies. Furthermore, with advancements in science and technology, carbon dioxide (CO2) is now considered a valuable raw material for producing carbon-based fuels through hydrogenation. Various concentrations of yttrium (referred to as Y hereafter) were introduced to assess their influence on the catalytic performance of CO2 methanation. At a temperature of 300 °C, the catalyst exhibited an impressive CO2 conversion rate of 78.4% and maintained remarkable stability throughout a rigorous 100 h stability assessment. The findings suggest that the inclusion of yttrium (Y) promotes the formation of oxygen vacancies and alkaline sites on the catalyst. This, in turn, enhances the reducibility of nickel species, improves the dispersion of nickel particles, and plays a pivotal role in enhancing thermal stability. Furthermore, it offers an innovative design approach for creating highly efficient composite CO2 methanation catalysts by controlling particle size and harnessing synergistic catalytic effects at the metal/support interface.

Recurrence and risk factors in cured patients with vitiligo: A real-life single-center retrospective study.

BACKGROUND: The risk of recurrence after successful repigmentation in vitiligo has attracted attention from both patients and clinicians. OBJECTIVES: The recurrence rate and risk factors in cured patients with vitiligo were analyzed to improve clinical prevention and treatment. METHODS: Clinical records of 76 patients with vitiligo who demonstrated at least 80% repigmentation were analyzed retrospectively. Single-factor analysis of variance and binary logistic regression analysis was employed to screen the risk factors of vitiligo recurrence. RESULTS: Among the 76 cured patients, 26 relapsed (total recurrence rate of 34.2%). Among these, 20 relapsed within one year (recurrence rate of 26.3%). Single-factor analysis of variance revealed significant differences (p < 0.05) with the age of onset (yr), distribution of onset, and oral traditional Chinese medicine (TCM) intake between the recurrence and nonrecurrence groups. Binary logistic regression analysis displayed that the age of onset (yr) (p = 0.015, OR = 1.051), distribution of onset (p = 0.046, OR = 0.194), and oral TCM (p = 0.018, OR = 4.360) are significant risk factors for vitiligo recurrence. CONCLUSION: A total relapse rate of 34.2% was observed in cured vitiligo patients. The age of onset (yr), distribution of onset, and oral TCM are risk factors for vitiligo recurrence. The necessary interventions should be considered on these factors for reducing the recurrence rate of vitiligo.

Establishment and characterization of two Epstein-Barr virus-positive gastric cancer cell lines with epitheliotropic M81 strain undergoing distinct viral and altered cellular expression profiles.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer (GC) distinguished by the presence of the EBV genome and limited viral gene expression within malignant epithelial cells. EBV infection is generally thought to be a relatively late event following atrophic gastritis in carcinogenesis, which implies the heterogeneity of EBVaGC. To facilitate the study of the role of EBV in EBVaGC, we established two EBV-positive GC cell lines (AGS-EBV and HGC27-EBV) with an epitheliotropic EBV strain M81 and characterized viral and cellular gene expression profiles in comparison to SNU719, a naturally derived EBV-positive GC cell line. Like SNU719, AGS-EBV and HGC27-EBV stably maintained their EBV genomes and expressed EBV-encoded small RNAs and nuclear antigen EBNA1. Comprehensive analysis of the expression of EBV-encoded miRNAs within the BamHI-A region rightward transcript region, and the transcripts of EBV latent and lytic genes in cell lines, as well as xenografts, reveals that AGS-EBV and HGC27-EBV cells undergo distinct viral expression profiles. A very small fraction of AGS-EBV and SNU719 cells can spontaneously produce infectious progeny virions, while HGC27-EBV does not. AGS-EBV (both M81 and Akata) cells largely mimic SNU719 cells in viral gene expression profiles, and altered cellular functions and pathways perturbed by EBV infection. Phylogenetic analysis of the EBV genome shows both M81 and Akata EBV strains are closely related to clinical EBVaGC isolates. Taken together, these two newly established EBV-positive GC cell lines can serve as models to further investigate the role of EBV in different contexts of gastric carcinogenesis and identify novel therapeutics against EBVaGC.

AMPK Promotes Larval Metamorphosis of Mytilus coruscus.

Metamorphosis is a critical process in the transition from planktonic life to benthic life for marine invertebrates, which is accompanied by a large amount of energy consumption. Previous studies have proved that AMP-activated protein kinase (AMPK), as a vital energy regulator, plays a prominent role in mediating the growth and development of terrestrial animals. However, its function in the growth and development of marine invertebrates, especially in metamorphosis, remains elusive. This study explored the function of AMPK in the larval metamorphosis of Mytilus coruscus. The full-length cDNA of AMPK genes in M. coruscus was cloned and characterized, which is composed of three subunits, McAMPKα, McAMPKß, and McAMPKγ. Pharmacological tests demonstrated that through the application of an AMPK activator, AMP substantially enhanced the larval metamorphosis rate (p < 0.05). By contrast, the larval metamorphosis rate decreased significantly after being treated with the AMPK inhibitor Compound C (p < 0.05). McAMPK gene knock-down resulted in a reduction in McAMPK gene expression (p < 0.05), and the larval metamorphosis of M. coruscus was significantly restrained (p < 0.05). These results indicated that AMPK signaling is vital in the larval metamorphosis of M. coruscus, which advances further understanding in exploring the molecular mechanisms in the metamorphosis of marine invertebrate larvae.

Acupuncture for cancer-related conditions: An overview of systematic reviews.

BACKGROUND: Acupuncture is commonly used for cancer-related conditions worldwide, and evidence is increasing year on year. There is a need to summarize the evidence of acupuncture for cancer-related conditions comprehensively and critically. OBJECTIVE: To evaluate and summarize the systematic reviews (SRs) that assess the effects and safety of acupuncture for cancer-related conditions, and to inform clinical practice and future studies. METHODS: A comprehensive search was conducted on Pubmed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Sinomed, and Wanfang from their inception to October 16, 2021. SRs of randomized controlled trials (RCTs) on acupuncture for cancer-related conditions were to be included. Two reviewers screened the eligible articles, and four reviewers in pair extracted data and assessed the methodological quality/risk of bias of all included reviews by AMSTAR 2 and ROBIS tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a summary of meta-analysis or narrative description. RESULTS: Fifty-one SRs of RCTs on acupuncture for cancer-related conditions were included and synthesized. The methodological quality of SRs included 1 "high", 5 "low" and 45 "very low" by AMSTAR 2. Sixteen SRs assessed as low risk of bias (31.37%), and 35 SRs had high risk of bias (68.63%) by ROBIS. Acupuncture showed effective on systemic conditions in relation to different cancers, including cancer-related pain (17 SRs, 80 RCTs), fatigue (7 SRs, 18 RCTs), insomnia (4 SRs, 10 RCTs), quality of life (2 SRs, 15 RCTs); conditions in relation to chemo-radiotherapy, including nausea and vomiting (3 SRs, 36 RCTs) and bone marrow suppression (2 SRs, 21 RCTs); and conditions in relation to specific cancers, including breast cancer-related menopause (3 SRs, 6 RCTs), hot flashes (12 SRs, 13 RCTs), arthralgia (5 SRs, 10 RCTs), and nasopharyngeal cancer-related dysphagia (1 SRs, 7 RCTs). Acupuncture appeared to have benefit for patients with lymphoedema (3 SRs, 3 RCTs), gastrointestinal function (5 SRs, 27 RCTs), and xerostomia (4 SRs, 7 RCTs). Limited evidence showed inconsistent results on acupuncture for chemotherapy-induced peripheral neuropathy (3 SRs, 6 RCTs), depression and anxiety (3 SRs, 9 RCTs). Acupuncture was regarded as a safe therapy for cancer patients as no severe adverse events related were reported. CONCLUSION: Evidence from SRs showed that acupuncture is beneficial to cancer survivors with cancer-related pain, fatigue, insomnia, improved quality of life, nausea and vomiting, bone marrow suppression, menopausal symptoms, arthralgia, and dysphagia, and may also be potential for lymphoedema, gastrointestinal function, and xerostomia. For neuropathy, depression and anxiety, acupuncture should be used as an option based on individual conditions. Acupuncture is relatively safe without serious adverse events. More well-designed clinical trials of acupuncture are recommended on cancer-related depression and anxiety, arthralgia, xerostomia, gastrointestinal dysfunction and dysphagia.

[Design, manufacture and evaluation of a multi-parameter controllable automatic fire-acupuncture instrument].

A multi-parameter controllable automatic fire-acupuncture instrument was developed by integrating traditional fire needling with modern medical device technology. A gun-like appearance was designed for easy hand-held operation, the electromagnetic induction was for heating needle body, a scale knob was for controlling the needle insertion depth, the combination of electromagnetic ejection and spring return was for the precise control of the needle retention time; and the changeable single ste-rile needle or multiple needles were adopted to meet individual demand, obtain high efficiency and prevent infection. All of these designs are associated with the overall process control system to ensure the exact controllability of needle body temperature, needling density, insertion depth and needle retention time. Besides, this device is advantageous at handy and aseptic operation with high efficiency, conformability and visualization. In this research, this instrument was tested in animals for the impacts of automatic fire needling on skin damage and fur growth. It is found that the accurate control of each parameter is of the significant advantage in the safety and effectiveness of treatment, which lays a solid foundation for the subsequent systematic review on safety and effectiveness.

An Arabidopsis Retention and Splicing complex regulates root and embryo development through pre-mRNA splicing.

Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.

Experimental Research on Seepage Law and Migration Characteristics of Core-Shell Polymeric Nanoparticles Dispersion System in Porous Media.

The nanoparticles dispersion system has complex migration characteristics and percolation law in porous media due to the interaction between the nanoparticles and porous media. In this paper, lab experiments were carried out to characterize the morphology, particle size distributions, and apparent viscosities of SiO2/P(MBAAm-co-AM) polymeric nanoparticle solution, investigate its migration characteristics in porous media, and probe its capability of enhanced oil recovery (EOR) in the reservoirs. Quartz microtubule, sand pack, and etched glass micromodels were used as the porous media in the flow and flooding experiments. Gray image-processing technology was applied to achieve oil saturation at different flooding stages in the micromodel for calculating the EOR of the SiO2/P(MBAAm-co-AM) polymeric nanoparticle solution. The results show that The SiO2/P(MBAAm-co-AM) polymeric nanoparticles are spherical with diameters ranging from 260 to 300 nm, and the thicknesses of the polymeric layers are in the range of 30-50 nm. As the swelling time increases from 24 to 120 h, the medium sizes of the SiO2/P(MBAAm-co-AM) polymeric nanoparticles increase from 584.45 to 1142.61 nm. The flow of the SiO2/P(MBAAm-co-AM) polymeric nanoparticles has obvious nonlinear characteristics and a prominent scale effect at a low-pressure gradient, and there should be an optimal matching relationship between its injection mass concentration and the channel size. The flow tests in the sand packs demonstrate that the SiO2/P(MBAAm-co-AM) polymeric nanoparticles can form effective plugging in the main flow channels at different permeability areas and can break through at the throat to fulfill the step-by-step profile control. Moreover, the profile control of the SiO2/P(MBAAm-co-AM) polymeric nanoparticles strengthens with an increase in their swelling time. The microscopic flooding experiment in the etched glass micromodel confirms that the SiO2/P(MBAAm-co-AM) polymeric nanoparticles can block dynamically and alternatively the channels of different sizes with the form of loose or dense networks to adjust the fluid flow diversion, improve the sweep efficiency, and recover more residual oil. The SiO2/P(MBAAm-co-AM) polymeric nanoparticles can achieve an enhanced oil recovery of 20.71% in the micromodel.

Micro-Injury Induces Hair Regeneration and Vitiligo Repigmentation Through Wnt/ß-Catenin Pathway.

Extrinsic injury can evoke intrinsic stimulation and subsequently initiate the physiological repair process. This study aims to investigate whether clinically acceptable micro-injury could be used to create local stimuli to induce hair regeneration and vitiligo repigmentation. A novel device was designed and manufactured to precisely control the micro-injury parameters. Then the most appropriate extent of micro-injury without over-damaging the skin was evaluated. Finally, the effects of micro-injury on hair regeneration and vitiligo repigmentation were examined by macroscopic observation, histological staining, gene and protein expression analysis. We discover that proper micro-injury effectively induces hair regeneration by activating the hair follicle stem cell proliferation and migration downwards to the hair matrix, finally shifting the hair follicle stage from telogen into anagen. On vitiligo model mice, micro-injury also induces the hair follicle melanocyte stem cells to migrate upwards to the interfollicular epidermis, activating and giving rise to melanocytes to repopulate the vitiligo lesion. Mechanistic analysis indicates that the canonical Wnt/ß-catenin pathway plays a key role in the micro-injury-induced repair process. This study demonstrates that micro-injury has great potential in inducing hair regeneration and vitiligo repigmentation, laid a foundation to develop a micro-injury-based treatment method in alopecia and vitiligo.

Assessment of the Multiphase Mechanical Properties of the Longmaxi Formation Shale Using Nanoindentation Tests.

Mechanical properties are some of the most important parameters for understanding well drilling and hydraulic fracturing designs in unconventional reservoir development. As an effective tool, nanoindentation has been used to determine the mechanical properties of rocks at the nanoscale. In this study, the Longmaxi Formation shale samples from the Yibin area of China were collected and analyzed to obtain the multiphase mechanical properties. The mineral compositions and organic geochemistry of the shale samples were studied using X-ray diffraction, energy-dispersive X-ray spectrometry, and a carbon/sulfur analyzer. The pore structures of the shale samples at the micro- and nanoscales were characterized by field-emission scanning electron microscopy. The mechanical parameters of the shale samples, such as the hardness and elastic modulus, were investigated using the nanoindentation method to identify three mineral phases: brittle minerals, soft matters, and complex minerals at the interfaces between brittle minerals and soft matters. The uncertainty characteristics of the mechanical parameters of the three mineral phases were evaluated using the Weibull model, and the factors interfering with the mechanical parameters were analyzed for the different shale samples. The results showed that the brittle minerals had the largest recovered elastic deformations and the smallest residual deformations, while the soft matters had the largest residual deformations and the smallest recovered elastic deformations. The analysis results of the coefficients of variation and the Weibull modulus both confirmed that the scatter of the hardness was higher than that of the elastic modulus because of the uncertain contact area, and the hardness and elastic modulus of the soft matters had the highest uncertainty among the three mineral phases. The elastic modulus increased nonlinearly with increasing hardness according to a power function for the whole shale sample. The elastic modulus and hardness both had a favorable linear relationship with the total organic carbon (TOC) content, illustrating that the TOC content was one of the significant factors that affected the mechanical parameters of the shale samples.

Targeting the SHP2 phosphatase promotes vascular damage and inhibition of tumor growth.

The tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and SHP2 inhibition reduces tumor growth. Here, we report that SHP2 is an essential promoter of endothelial cell survival and growth in the remodeling tumor vasculature. Using genetic and chemical approaches to inhibit SHP2 activity in endothelial cells, we show that SHP2 inhibits pro-apoptotic STAT3 and stimulates proliferative ERK1/2 signaling. Systemic SHP2 inhibition in mice bearing tumor types selected for SHP2-independent tumor cell growth promotes degeneration of the tumor vasculature and blood extravasation; reduces tumor vascularity and blood perfusion; and increases tumor necrosis. Reduction of tumor growth ensues, independent of SHP2 targeting in the tumor cells, blocking immune checkpoints, or recruiting macrophages. We also show that inhibiting the Angiopoietin/TIE2/AKT cascade magnifies the vascular and anti-tumor effects of SHP2 inhibition by blocking tumor endothelial AKT signaling, not a target of SHP2. Since the SHP2 and Ang2/TIE2 pathways are active in vascular endothelial cells of human melanoma and colon carcinoma, SHP2 inhibitors alone or with Ang2/TIE2 inhibitors hold promise to effectively target the tumor endothelium.