New clinical classification of stiff skin syndrome.

BACKGROUND: Stiff skin syndrome (SSS) is a rare disease characterized by thickened, indurated skin and limited joint movement. Multiple diverse phenotypes have been reported, and the correlation of severity with the clinical heterogeneity and histopathological findings of SSS needs to be refined. OBJECTIVE: To define subtypes based on clinical features and predict the prognosis of a new SSS classification. METHODS: Eighty-three patients with SSS were retrospectively reviewed for clinicopathological manifestations and routine laboratory workup, including 59 cases obtained from a PubMed search between 1971 and 2022 and 24 cases diagnosed in our department between 2003 and 2022. RESULTS: Among the 83 patients, 27.7, 41, and 31.3% had classic widespread, generalized segmental, and localized SSS, respectively. Joint immobility was present in 100, 71, and 20% of classic, generalized, and localized cases, respectively. Histopathologic findings were common among the 3 groups, and based on that, we further found a difference in the distribution of proliferative collagen. 54.5% of classic and 50% of generalized cases occurred throughout the dermis or the subcutis, whereas 76% of localized cases were mainly involved in the reticular dermis or subcutis. In patients with incipient localized SSS, 42% (21/50) developed generalized SSS, and only 6% (3/50) progressed to classic SSS, whereas more than half of the incipient generalized SSS cases (60.6%, 20/33) developed classic SSS. LIMITATIONS: This retrospective study was limited to previously published cases with limited data. CONCLUSIONS: We propose a distinct clinical classification characterized by lesion distribution, including classic widespread, generalized segmental, and localized SSS, associated with disease severity and prognosis.

Lipidomics profile and volatile compounds of squids (Illex argentinus, Ommastrephes Bartram and Dosidicus gigas) in the Argentine, North Pacific Ocean, Equator and Peru by UPLC-triple TOF-MS and HS-SPME-GC-O-MS.

Comprehensive lipid and volatile compound analyses were performed with squids collected from four varied geographical locations to discriminate the regional characteristics. A total of 1442 lipid molecules and 110 volatiles were detected in the squid muscle samples. There were significant differences in the lipid profiles between Argentine squid (Illex argentinus, AGT), North Pacific Ocean squid (Ommastrephes Bartram, NPO), Equatorial squid (Dosidicus gigas, EQ), and Peruvian squid (Dosidicus gigas, PR) muscle. Phosphatidylcholines (14.64%), triacylglycerols (12.42%), and ceramides (10.97%) were the main lipid components. The contents of polyunsaturated fatty acid in phospholipids and in glycerolipids were 30.35-52.05% and 18.11-25.15%, respectively. The volatiles in squids exhibited significant regional variation; 1-pentanol and 1-octanol, 2-ethyl-1-hexanol and terpinen-4-ol, 2,7-ethyl-1-hexanol, 3-methy-1-butanol and 2-propyl-1-pentanol were identified as characteristic flavor compounds in AGT, NPO, EQ, and PR, respectively. Sphingomyelin, phosphatidylserine, phosphatidylethanolamine, and ceramide were strongly correlated with volatiles in squid muscle. Our study is a reference for the lipid nutritional value and flavor compounds of squids.

Efficacy and safety of tirofiban in patients with acute branch atheromatous disease-related stroke (BRANT): a protocol for a randomised controlled trial.

INTRODUCTION: Branch atheromatous disease (BAD)-related stroke is increasingly becoming a clinical entity and prone to early neurological deterioration (END) and poor prognosis. There are no effective regimens to reduce the disability caused by BAD-related stroke in acute phase. Recent studies have indicated the efficacy of tirofiban in acute ischaemic stroke; however, its efficacy has not been validated in patients with BAD-related stroke. Thus, we aim to test whether intravenous tirofiban initiated within 48 hours after the onset would improve the functional outcome in patients with acute BAD-related stroke, in comparison with the standard antiplatelet therapy based on the current guideline. METHODS AND ANALYSIS: BRANT is a multicentre, randomised, open-label, blinded endpoint, parallel-controlled, phase III trial conducted in 21 hospitals in China. Participants aged 18-75 years with acute BAD-related stroke within 48 hours after the stroke onset are randomised in a 1:1 ratio to the tirofiban or control group. The treatment period is 48 hours in both groups. The primary outcome is the excellent functional outcome (modified Rankin Scale Score: 0-1) at 90 days. The secondary outcomes include END, major bleeding, stroke, death, functional status, serious adverse events and change in bleeding-related markers. Assuming the rates of the primary outcome to be 74% in the tirofiban group and 62% in the control group, a total of 516 participants are needed for 0.8 power (two-sided 0.05 alpha). ETHICS AND DISSEMINATION: BRANT study has been approved by the Ethics Committee of the Peking Union Medical College Hospital (I-23PJ1242). Written informed consent is required for all the patients before enrolment. The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT06037889).

The genetic risk factors for cerebral venous thrombosis: a case-control study in a Chinese national comprehensive hospital.

BACKGROUND: About 13-25% of cerebral venous thrombosis (CVT) cases lack clear etiology, which may be associated with underlying genetic factors. This study aims to investigate genetic factors in CVT patients using whole exome sequencing (WES). METHODS: Thirty-eight CVT patients hospitalized underwent WES. 977 subjects with WES data from a community cohort study --the Shunyi cohort were as the control group. Using bioinformatics analysis, differential genes with rare damaging variants between two groups were filtered (P < 0.05). KEGG enrichment analysis was performed on the screened genes to identify pathways associated with CVT. RESULTS: Through analysis of medical history, routine tests, and imaging examinations, the etiology of 38 patients: 8 cases of antiphospholipid syndrome, 6 cases with hematologic diseases, 3 cases of protein C deficiency, and 2 cases of protein S deficiency. Five cases occurred during pregnancy or puerperium, and 3 cases had a history of oral contraceptive use, and so on. The etiology was unknown in 12 cases (31.6%), and the etiology of 4 patients were further clarified through WES: F9 c.838 + 1_838 + 16del, Hemizygote: F9 EX1-EX7 Dup; CBS c.430G > A, CBS c.949 A > G; F2 c.1787G > A; SERPINC1 c.409-11G > T. Comparing the WES data of two groups, a total of 179 different genes with rare damaging variants were screened (P < 0.05), with 5 genes of interest (JAK2, C3, PROC, PROZ, SERPIND1). Enrichment analysis of the 179 different genes revealed the complement and coagulation pathway and the mitogen activated protein kinases (MAPK) pathway were associated with CVT. CONCLUSION: For CVT patients with unknown etiology, WES could help identify the cause of CVT early, which is of great significance for treatment decisions and prognosis. In addition to the complement and coagulation pathway, MAPK pathway is associated with CVT, potentially related to platelet regulation and inflammatory response.

The risk profiles of pregnancy-related cerebral venous thrombosis: a retrospective study in a comprehensive hospital.

OBJECTIVES: To investigate the risk factors and underlying causes of pregnancy-related cerebral venous thrombosis (PCVT). METHODS: A retrospective cohort of 16 patients diagnosed with CVT during pregnancy and postpartum (within six weeks after delivery) in a comprehensive hospital in China between 2009 and 2022 were carefully reviewed, focusing on demographic, clinical, and etiological characteristics, especially underlying causes. We matched 16 PCVT patients with 64 pregnant and puerperal women without PCVT to explore risk factors and clinical susceptibility to PCVT. RESULTS: PCVT occurred commonly during the first trimester (43.75%) and the puerperium (37.5%). The frequency of anemia, thrombocytosis and thrombocytopenia during pregnancy, dehydration, and pre-pregnancy anemia was significantly higher in women with PCVT than in those without PCVT (P < 0.05). Among the 16 patients, five were diagnosed with antiphospholipid syndrome and one was diagnosed with systemic lupus erythematosus. Three patients had distinct protein S deficiency and one had protein C deficiency. Whole Exome Sequencing (WES) was performed for five patients and revealed likely pathogenic mutations associated with CVT, including heterozygous PROC c.1218G > A (p. Met406Ile), heterozygous PROS1 c.301C > T (p. Arg101Cys), composite heterozygous mutation in the F8 gene (c.144-1259C > T; c.6724G > A (p. Val2242Met)) and homozygous MTHFR c.677C > T (p. Ala222Val). CONCLUSIONS: The occurrence of anemia, thrombocytopenia and thrombocytosis during pregnancy, dehydration and pre-pregnancy anemia suggested a greater susceptibility to PCVT. For confirmed PCVT patients, autoimmune diseases, hereditary thrombophilia, and hematological disorders were common causes. Screening for potential etiologies should be paid more attention, as it has implications for treatment and long-term management.

Clinical characteristics of cerebral amyloid angiopathy and risk factors of cerebral amyloid angiopathy related intracerebral hemorrhage.

OBJECTIVES: There is limited understanding of the differences between cerebral amyloid angiopathy (CAA) with and without intracerebral hemorrhage (ICH). This article aimed to describe the characteristics of CAA and identify the risk factors of CAA-ICH in a multicenter cohort. METHODS: Patients consecutively enrolled in the national multicenter prospective Cerebral Small Vessel Disease Cohort Study who met the Boston diagnostic criteria for CAA or CAA-related inflammation were included in this study. The demographic characteristics and clinical data were collected. The clinical and radiographic differences between CAA with and without ICH were compared to identify the risk factors for CAA-ICH. RESULTS: A total of 219 CAA patients were included, with an average age of 67.12 ± 9.93. Of all patients, 26.0% were CAA with ICH. Univariate analysis showed that CAA-ICH is associated with carrying more APOE ε2 allele, less lobar cerebral microbleeds (CMBs), cortical superficial siderosis (cSS), lower Fazekas scale, a tendency of gait disorder, and acute onset (P < 0.05). The generalized linear mixed model yielded statistically significant associations between CAA with ICH and carrying the APOE ε2 allele, cSS, the lower number of lobar CMBs, and the lower Fazekas scale (P < 0.05). CONCLUSION: It is meaningful to classify CAA with and without ICH, as there may be different mechanisms between the two. CAA with ICH has a susceptibility to carrying APOE ε2, cSS, and a relatively small number of CMBs. Fewer CMBs do not mean lower susceptibility to ICH in CAA. Larger prospective cohort studies are necessary to further clarify these conclusions.

The association between anxiety and internet addiction among left-behind secondary school students: the moderating effect of social support and family types.

BACKGROUND: The left-behind children (LBC), children and adolescents aged 0-18 whose parents have migrated for economic purposes for extended periods exceeding three months, present a unique social concern. These children remain in their place of household registration, often under the guardianship of relatives, while receiving compulsory education. LBC with growing Internet addiction (IA) have made it urgent to take a close look at the mechanisms and effective interventions for them. Anxiety has been proven to be correlated with IA in adolescents; however, the mechanisms of addiction in this population are less well-fully grasped. Based on the current theories and empirical results, the study examined whether and how social support (SS) and family types moderated the associations between anxiety and IA among left-behind secondary students. METHODS: Stratified cluster sampling survey. A questionnaire was administered to 5290 secondary school children (2553 classified as left-behind) to explore the relationships between anxiety, IA, left-behind types, family types, and social support. This cross-sectional study employed a stratified cluster sampling survey of students in the ethnic areas of southeast Chongqing. The study sought to appraise the relationships between anxiety and IA in different types of left-behind children and to assess the potential moderating effect of SS on the relationship among the population and its family types differences. RESULTS: The relationship between anxiety and IA was moderated significantly by social support and family types. Notably, the impact of social support on the moderating effect between IA and anxiety varied among students from both family types. For students from families where both parents had migrated, social support weakened the association between IA and anxiety. Conversely, for students from single-parent families where the parent had migrated, social support seemed to strengthen the relationships between these two issues. CONCLUSIONS: The moderating effects of SS on the relationship between anxiety and IA differs based on family type among various groups of left-behind secondary students. Gaining insights into the IA mechanisms can guide the development of targeted intervention strategies aimed at minimizing IA among diverse groups of left-behind students.

Remarkable flexibility in freestanding single-crystalline antiferroelectric PbZrO3 membranes.

The ultrahigh flexibility and elasticity achieved in freestanding single-crystalline ferroelectric oxide membranes have attracted much attention recently. However, for antiferroelectric oxides, the flexibility limit and fundamental mechanism in their freestanding membranes are still not explored clearly. Here, we successfully fabricate freestanding single-crystalline PbZrO3 membranes by a water-soluble sacrificial layer technique. They exhibit good antiferroelectricity and have a commensurate/incommensurate modulated microstructure. Moreover, they also have good shape recoverability when bending with a small radius of curvature (about 2.4 µm for the thickness of 120 nm), corresponding to a bending strain of 2.5%. They could tolerate a maximum bending strain as large as 3.5%, far beyond their bulk counterpart. Our atomistic simulations reveal that this remarkable flexibility originates from the antiferroelectric-ferroelectric phase transition with the aid of polarization rotation. This study not only suggests the mechanism of antiferroelectric oxides to achieve high flexibility but also paves the way for potential applications in flexible electronics.

ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and regulates the Warburg effect in breast cancer.

Pyruvate kinase M2 (PKM2) is a central metabolic enzyme driving the Warburg effect in tumor growth. Previous investigations have demonstrated that PKM2 is subject to O-linked ß-N-acetylglucosamine (O-GlcNAc) modification, which is a nutrient-sensitive post-translational modification. Here we found that unc-51 like autophagy activating kinase 1 (ULK1), a glucose-sensitive kinase, interacts with PKM2 and phosphorylates PKM2 at Ser333. Ser333 phosphorylation antagonizes PKM2 O-GlcNAcylation, promotes its tetramer formation and enzymatic activity, and decreases its nuclear localization. As PKM2 is known to have a nuclear role in regulating c-Myc, we also show that PKM2-S333 phosphorylation inhibits c-Myc expression. By downregulating glucose consumption and lactate production, PKM2 pS333 attenuates the Warburg effect. Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growth in vivo. In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.

Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells.

OBJECTIVE: Research has shown that celastrol can effectively treat a variety of diseases, yet when passing a certain dosage threshold, celastrol becomes toxic, causing complications such as liver and kidney damage and erythrocytopenia, among others. With this dichotomy in mind, it is extremely important to find ways to preserve celastrol's efficacy while reducing or preventing its toxicity. METHODS: In this study, insulin-resistant HepG2 (IR-HepG2) cells were prepared using palmitic acid and used for in vitro experiments. IR-HepG2 cells were treated with celastrol alone or in combination with N-acetylcysteine (NAC) or ferrostatin-1 (Fer-1) for 12, 24 or 48 h, at a range of doses. Cell counting kit-8 assay, Western blotting, quantitative reverse transcription-polymerase chain reaction, glucose consumption assessment, and flow cytometry were performed to measure celastrol's cytotoxicity and whether the cell death was linked to ferroptosis. RESULTS: Celastrol treatment increased lipid oxidation and decreased expression of anti-ferroptosis proteins in IR-HepG2 cells. Celastrol downregulated glutathione peroxidase 4 (GPX4) mRNA. Molecular docking models predicted that solute carrier family 7 member 11 (SLC7A11) and GPX4 were covalently bound by celastrol. Importantly, we found for the first time that the application of ferroptosis inhibitors (especially NAC) was able to reduce celastrol's toxicity while preserving its ability to improve insulin sensitivity in IR-HepG2 cells. CONCLUSION: One potential mechanism of celastrol's cytotoxicity is the induction of ferroptosis, which can be alleviated by treatment with ferroptosis inhibitors. These findings provide a new strategy to block celastrol's toxicity while preserving its therapeutic effects. Please cite this article as: Liu JJ, Zhang X, Qi MM, Chi YB, Cai BL, Peng B, Zhang DH. Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells. J Integr Med. 2024; 22(3): 286-294.

Analysis of sugar components and identification of SPS genes in citrus fruit development.

Sugar is a primary determinant of citrus fruit flavour, but undergoes varied accumulation processes across different citrus varieties owing to high genetic variability. Sucrose phosphate synthase (SPS), a key enzyme in glucose metabolism, plays a crucial role in this context. Despite its significance, there is limited research on sugar component quality and the expression and regulatory prediction of SPS genes during citrus fruit development. Therefore, we analysed the sugar quality formation process in 'Kiyomi' and 'Succosa', two citrus varieties, and performed a comprehensive genome-wide analysis of citrus CsSPSs. We observed that the accumulation of sugar components significantly differs between the two varieties, with the identification of four CsSPSs in citrus. CsSPS sequences were highly conserved, featuring typical SPS protein domains. Expression analysis revealed a positive correlation between CsSPS expression and sugar accumulation in citrus fruits. However, CsSPS expression displays specificity to different citrus tissues and varieties. Transcriptome co-expression network analysis suggests the involvement of multiple transcription factors in shaping citrus fruit sugar quality through the regulation of CsSPSs. Notably, the expression levels of four CsWRKYs (CsWRKY2, CsWRKY20, CsWRKY28, CsWRKY32), were significantly positively correlated with CsSPSs and CsWRKY20 might can activate sugar accumulation in citrus fruit through CsSPS2. Collectively, we further emphasize the potential importance of CsWRKYs in citrus sugar metabolism, our findings serve as a reference for understanding sugar component formation and predicting CsSPS expression and regulation during citrus fruit development.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

PARP1 UFMylation ensures the stability of stalled replication forks.

The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.

Long Non-Coding RNA Nuclear-Enriched Abundant Transcript 1 (NEAT1) Facilitates Foam Cell Formation and Atherosclerosis Progression Through the miR-17-5p/Itchy E3 Ubiquitin Protein Ligase (ITCH)/Liver Kinase B1 (LKB1) Axis.

BACKGROUND: Foam cell formation is an important step for atherosclerosis (AS) progression. We investigated the mechanism by which the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) regulates foam cell formation during AS progression.Methods and Results: An in vivo AS model was created by feeding ApoE-/-mice a high-fat diet. Oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages were used as a cellular AS model. Interactions between NEAT1, miR-17-5p, itchy E3 ubiquitin protein ligase (ITCH) and liver kinase B1 (LKB1) were analyzed. NEAT1 and ITCH were highly expressed in clinical samples collected from 10 AS patients and in ox-LDL-treated macrophages, whereas expression of both miR-17-5p and LKB1 was low. ITCH knockdown inhibited ox-LDL-induced lipid accumulation and LDL uptake in macrophages. Mechanistically speakingly, ITCH promoted LDL uptake and lipid accumulation in macrophages by mediating LKB1 ubiquitination degradation. NEAT1 knockdown reduced LDL uptake and lipid accumulation in macrophages and AS progression in vivo. NEAT1 promoted ITCH expression in macrophages by acting as a sponge for miR-17-5p. Inhibition of miR-17-5p facilitated ox-LDL-induced increase in LDL uptake and lipid accumulation in macrophages, which was reversed by NEAT1/ITCH knockdown. CONCLUSIONS: NEAT1 accelerated foam cell formation during AS progression through the miR-17-5p/ITCH/LKB1 axis.

Continuous planting of euhalophyte Suaeda salsa enhances microbial diversity and multifunctionality of saline soil.

Halophyte-based remediation emerges as a novel strategy for ameliorating saline soils, offering a sustainable alternative to conventional leaching methods. While bioremediation is recognized for its ability to energize soil fertility and structure, the complex interplays among plant traits, soil functions, and soil microbial diversity remain greatly unknown. Here, we conducted a 5-year field experiment involving the continuous cultivation of the annual halophyte Suaeda salsa in saline soils to explore soil microbial diversity and their relationships with plant traits and soil functions. Our findings demonstrate that a decline in soil salinity corresponded with increases in the biomass and seed yield of S. salsa, which sustained a consistent seed oil content of approximately 22% across various salinity levels. Significantly, prolonged cultivation of halophytes substantially augmented soil microbial diversity, particularly from the third year of cultivation. Moreover, we identified positive associations between soil multifunctionality, seed yield, and taxonomic richness within a pivotal microbial network module. Soils enriched with taxa from this module showed enhanced multifunctionality and greater seed yields, correlating with the presence of functional genes implicated in nitrogen fixation and nitrification. Genomic analysis suggests that these taxa have elevated gene copy numbers of crucial functional genes related to nutrient cycling. Overall, our study emphasizes that the continuous cultivation of S. salsa enhances soil microbial diversity and recovers soil multifunctionality, expanding the understanding of plant-soil-microbe feedback in bioremediation.IMPORTANCEThe restoration of saline soils utilizing euhalophytes offers a viable alternative to conventional irrigation techniques for salt abatement and soil quality enhancement. The ongoing cultivation of the annual Suaeda salsa and its associated plant traits, soil microbial diversity, and functionalities are, however, largely underexplored. Our investigation sheds light on these dynamics, revealing that cultivation of S. salsa sustains robust plant productivity while fostering soil microbial diversity and multifunctionality. Notably, the links between enhanced soil multifunctionality, increased seed yield, and network-dependent taxa were found, emphasizing the importance of key microbial taxa linked with functional genes vital to nitrogen fixation and nitrification. These findings introduce a novel understanding of the role of soil microbes in bioremediation and advance our knowledge of the ecological processes that are vital for the rehabilitation of saline environments.

A State-Dependent Elasto-Plastic Model for Hydrate-Bearing Cemented Sand Considering Damage and Cementation Effects.

In order to optimize the efficiency and safety of gas hydrate extraction, it is essential to develop a credible constitutive model for sands containing hydrates. A model incorporating both cementation and damage was constructed to describe the behavior of hydrate-bearing cemented sand. This model is based on the critical state theory and builds upon previous studies. The damage factor Ds is incorporated to consider soil degradation and the reduction in hydrate cementation, as described by plastic shear strain. A computer program was developed to simulate the mechanisms of cementation and damage evolution, as well as the stress-strain curves of hydrate-bearing cemented sand. The results indicate that the model replicates the mechanical behavior of soil cementation and soil deterioration caused by impairment well. By comparing the theoretical curves with the experimental data, the compliance of the model was calculated to be more than 90 percent. The new state-dependent elasto-plastic constitutive model based on cementation and damage of hydrate-bearing cemented sand could provide vital guidance for the construction of deep-buried tunnels, extraction of hydrocarbon compounds, and development of resources.

The effect of intelligent management interventions in intensive care units to reduce false alarms: An integrative review.

Objective: In intensive care units (ICU), frequent false alarms from medical equipment can cause alarm fatigue among nurses, which might lead to delayed or missed responses and increased risk of adverse patient events. This review was conducted to evaluate the effectiveness of intelligent management interventions to reduce false alarms in ICU. Method: Following the framework of Whitmore and Knafl, the reviewers systematically searched six databases: PubMed, EMBASE, CINAHL, OVID, Cochrane Library, and Scopus, and studies included intelligent management of clinical alarms published in the English or Chinese language from the inception of each database to December 2022 were retrieved. The researchers used the PICOS framework to formulate the search strategy, developed keywords, screened literature, and assessed the studies' quality using the Joanna Briggs Institute-Meta-Analysis of Statistics, Assessment, and Review Instrument (JBI-MAStARI). The review was preregistered on PROSPERO (CRD42023411552). Results: Seven studies met the inclusion criteria. The results showed that different interventions for intelligent management of alarms were beneficial in reducing the number of false alarms, the duration of alarms, the response time to important alarms for nurses, and the alarm fatigue levels among nurses. Positive results were found in practice after the application of the novel alarm management approaches. Conclusion: Intelligent management intervention may be an effective way to reduce false alarms. The application of systems or tools for the intelligent management of clinical alarms is urgent in hospitals. To ensure more effective patient monitoring and less distress for nurses, more alarm management approaches combined with artificial intelligence will be needed in the future to enable accurate identification of critical alarms, ensure nurses are responding accurately to alarms, and make a real difference to alarm-ridden healthcare environments.

Salinity inhibits seed germination and embryo growth by reducing starch mobilization efficiency in barley.

Barley is one of the world's earliest domesticated crops, which is widely used for beer production, animal feeding, and health care. Barley seed germination, particularly in increasingly saline soils, is key to ensure the safety of crop production. However, the mechanism of salt-affected seed germination in barley remains elusive. Here, two different colored barley varieties were used to independently study the regulation mechanism of salt tolerance during barley seed germination. High salinity delays barley seed germination by slowing down starch mobilization efficiency in seeds. The starch plate test revealed that salinity had a significant inhibitory effect on α-amylase activity in barley seeds. Further, NaCl treatment down-regulated the expression of Amy1, Amy2 and Amy3 genes in germinated seeds, thereby inhibiting α-amylase activity. In addition, the result of embryogenic culture system in vitro showed that the shoot elongation of barley was significantly inhibited by salt stress. These findings indicate that it is a feasible idea to study the regulation mechanism of salinity on barley seed germination and embryo growth from the aspect of starch-related source-sink communication.