Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma.

Clinically, the immune checkpoint inhibitor anti-PD-1 antibody has shown a certain effect in the treatment of hepatocellular carcinoma (HCC), which is limited to a small number of patients with HCC. This study aims to reveal whether carnosic acid nanocluster-based framework (CA-NBF) has a sensitization effect on anti-PD-1 antibody in the treatment of HCC at the cellular and animal levels. MHCC97H cells were treated with CA-NBF, anti-PD-1 and their combination. The effects of CA-NBF and anti-PD-1 on cell proliferation, cell cycle, apoptosis, invasion, and migration were evaluated by MTT assay, flow cytometry, and scratch test. The effects of CA-NBF and anti-PD-1 on Wnt/ß-catenin signaling pathway in MHCC97H cells were detected. A BALB/C nude mouse model of hepatocellular carcinoma was established, and the tumor growth was observed at different time points. The expression of cytotoxic T lymphocyte and helper T lymphocyte markers CD8 and CD4 in tumor tissues was detected by immunohistochemistry. Western blotting was used to detect the Wnt/ß-catenin signaling pathway proteins (Wnt-3a, ß-catenin, and GSK-3ß) level in tumor tissues after CA-NBF and anti-PD-1 treatment. CA-NBF activity was significantly higher than CA, which could prominently reduce the proliferation, migration and invasion of MHCC97H cells and enhance apoptosis by inactivating Wnt/ß-catenin signaling pathway. CA-NBF combined with anti-PD-1 antibody further enhanced cell proliferation, migration, invasion and pro-apoptosis but had no significant effect on Wnt/ß-catenin signaling pathway. CA-NBF in vivo improved the tumor response to PD1 immune checkpoint blockade in HCC, manifested by reducing tumor size and weight, promoting CD4 and CD8 expression. CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.

Anastrozole for the prevention of breast cancer in high-risk postmenopausal women: cost-effectiveness analysis in the UK and the USA.

PURPOSE: The effectiveness of anastrozole for breast cancer prevention has been demonstrated. The objective of this study was to evaluate the cost-effectiveness of anastrozole for the prevention of breast cancer in women with a high risk of breast cancer and to determine whether anastrozole for the primary prevention of breast cancer can improve the quality of life of women and save health-care resources. METHODS: A decision-analytic model was used to assess the costs and effects of anastrozole prevention versus no prevention among women with a high risk of breast cancer. The key parameters of probability were derived from the IBIS-II trial, and the cost and health outcome data were derived from published literature. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for the two strategies,One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental cost per QALY of anastrozole prevention was £125,705.38/QALY in the first 5 years compared with no prevention in the UK, above the threshold of WTP (£3,000/QALY),and in the 12-year period, the ICER was £8,313.45/QALY, less than WTP. For the US third-party payer, ICER was $134,232.13/QALY in the first 5 years and $8,843.30/QALY in the 12 years, both less than the WTP threshold ($150,000/QALY). CONCLUSION: In the UK and US, anastrozole may be a cost-effective strategy for the prevention of breast cancer in high-risk postmenopausal women. Moreover, the longer the cycle of the model, the higher the acceptability. The results of this study may provide a scientific reference for decision-making for clinicians, patients, and national medical and health care government departments.

Effectiveness and tolerability of camrelizumab combined with molecular targeted therapy for patients with unresectable or advanced HCC.

There is a lack of effective programmed cell death protein 1 (PD-1)-targeted immunotherapy with good tolerability in patients with advanced hepatocellular carcinoma (HCC) and severely compromised liver function. We assessed patient outcomes after combined camrelizumab and molecular targeted therapy in a multicenter cohort study in China. The study included 99 patients with advanced HCC (58 Child-Pugh A and 41 Child-Pugh B), 84 of them received camrelizumab combined with molecular targeted therapy from January 10, 2019, to March 31, 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were assessed. The median follow-up was 12.1 months. For patients with Child-Pugh B, the OS probability at 12-months, ORR and DCR were 49.7%, 31.7% and 65.9%, respectively, and the median PFS was 5.1 months [95% confidence interval (CI) 3.0-7.1], which were comparable with Child-Pugh A patients, although median OS was shorter in Child-Pugh B patients (20.5 vs.13.4 months, P = 0.12). In multivariate analysis, macrovascular infiltration (MVI), but not sex, age, hepatitis B virus etiology, extrahepatic metastasis, Child-Pugh B, or AFP > 400 ng/ml, was associated with 12-months OS [hazard ratio (HR) 2.970, 95% CI 1.276-6.917, P = 0.012] and ORR (HR 2.906, 95% CI 1.18-7.16, P = 0.020). Grade 3/4 immune-related AEs occurred in 26.8% of Child-Pugh B patients, including one potentially treatment-related death. In both groups, the most common AEs were immune thrombocytopenia and hepatotoxicity. Camrelizumab combined with targeted therapy showed favorable effectiveness and tolerability with manageable toxicities in Chinese HCC patients, regardless of Child-Pugh A/B liver function. MVI was associated with suboptimal immunotherapy response and poor prognosis.

Searching for Afterglow: Light Dark Matter Boosted by Supernova Neutrinos.

A novel analysis is performed, incorporating time-of-flight (TOF) information to study the interactions of dark matter (DM) with standard model particles. After supernova (SN) explosions, DM with mass m_{χ}≲O(MeV) in the halo can be boosted by SN neutrinos (SNν) to relativistic speed. The SNν boosted DM (BDM) arrives on Earth with TOF which depends only on m_{χ} and is independent of the cross section. These BDMs can interact with detector targets in low-background experiments and manifest as afterglow events after the arrival of SNν. The characteristic TOF spectra of the BDM events can lead to large background suppression and unique determination of m_{χ}. New cross section constraints on sqrt[σ_{χe}σ_{χν}] are derived from SN1987a in the Large Magellanic Cloud with data from the Kamiokande and Super-Kamiokande experiments. Potential sensitivities for the next galactic SN with Hyper-Kamiokande are projected. This analysis extends the existing bounds on sqrt[σ_{χe}σ_{χν}] over a broad range of r_{χ}=σ_{χν}/σ_{χe}. In particular, the improvement is by 1-3 orders of magnitude for m_{χ}

Regulatory network of rice in response to heat stress and its potential application in breeding strategy.

The rapid development of global industrialization has led to serious environmental problems, among which global warming has become one of the major concerns. The gradual rise in global temperature resulted in the loss of food production, and hence a serious threat to world food security. Rice is the main crop for approximately half of the world's population, and its geographic distribution, yield, and quality are frequently reduced due to elevated temperature stress, and breeding rice varieties with tolerance to heat stress is of immense significance. Therefore, it is critical to study the molecular mechanism of rice in response to heat stress. In the last decades, large amounts of studies have been conducted focusing on rice heat stress response. Valuable information has been obtained, which not only sheds light on the regulatory network underlying this physiological process but also provides some candidate genes for improved heat tolerance breeding in rice. In this review, we summarized the studies in this field. Hopefully, it will provide some new insights into the mechanisms of rice under high temperature stress and clues for future engineering breeding of improved heat tolerance rice.

Characterization of Dof Transcription Factors and the Heat-Tolerant Function of PeDof-11 in Passion Fruit (Passiflora edulis).

Abiotic stress is the focus of passion fruit research since it harms the industry, in which high temperature is an important influencing factor. Dof transcription factors (TFs) act as essential regulators in stress conditions. TFs can protect against abiotic stress via a variety of biological processes. There is yet to be published a systematic study of the Dof (PeDof) family of passion fruit. This study discovered 13 PeDof family members by using high-quality genomes, and the members of this characterization were identified by bioinformatics. Transcriptome sequencing and qRT-PCR were used to analyze the induced expression of PeDofs under high-temperature stress during three periods, in which PeDof-11 was significantly induced with high expression. PeDof-11 was then chosen and converted into yeast, tobacco, and Arabidopsis, with the findings demonstrating that PeDof-11 could significantly respond to high-temperature stress. This research lays the groundwork for a better understanding of PeDof gene regulation under high-temperature stress.

MiR-34b/c play a role in early sex differentiation of Amur sturgeon, Acipenser schrenckii.

BACKGROUND: Sex differentiation can be viewed as a controlled regulatory balance between sex differentiation-related mRNAs and post-transcriptional mechanisms mediated by non-coding RNAs. In mammals, increasing evidence has been reported regarding the importance of gonad-specific microRNAs (miRNAs) in sex differentiation. Although many fishes express a large number of gonadal miRNAs, the effects of these sex-biased miRNAs on sex differentiation in teleost fish remain unknown. Previous studies have shown the exclusive and sexually dimorphic expression of miR-34b/c in the gonads of the Amur sturgeon (Acipenser schrenckii), suggesting its potential role in the sex differentiation process. RESULTS: Using quantitative real-time PCR (qPCR), we observed that miR-34b/c showed consistent spatiotemporal expression patterns; the expression levels significantly increased during early sex differentiation. Using in situ hybridization, miR-34c was found to be located in the germ cells. In primary germ cells in vitro, the group subjected to overexpression and inhibition of miR-34c showed significantly higher proliferation ability and lower apoptosis, respectively, compared to the corresponding control group. Luciferase reporter assays using the ar-3'UTR-psiCHECK-2 luciferase vector suggested a targeted regulatory interaction between miR-34b/c and the 3'UTR of the androgen receptor (ar) mRNA. Furthermore, miR-34b/c and ar showed negative expression patterns during early sex differentiation. Additionally, a negative feedback regulation pattern was observed between foxl2 expression in the ovaries and amh and sox9 expression in the testes during early sex differentiation. CONCLUSIONS: This study sheds new light on the roles of miR-34b/c in gonad development of Amur sturgeon, and provides the first comprehensive evidence that the gonad-predominant microRNAs may have a major role in sex differentiation in teleost fish.

Effect of intracutaneous pyonex on analgesia and sedation in critically ill patients with mechanical ventilation.

The purpose of this study was to evaluate the effect of intracutaneous pyonex on analgesia and sedation in critically ill patients who underwent mechanical ventilation. A total of 88 critically ill patients were divided into a control group and an intervention group. Critical Care Pain Observation Tool (CPOT) and Richmond Agitation and Sedation Scale (RASS) were used to evaluate pain and agitation. The dosage and treatment period of sedative and analgesic drugs in the intervention group were notably lower than the control group (p < 0.05). Analgesia compliance time in the intervention group was superior to control group (p < 0.05). The shallow sedation compliance rate in the intervention group was significantly higher than the control group (p < 0.01). There was significant difference in blood gas analysis before and after treatment between the two groups (p < 0.05). After 2 h of sedation and analgesia, heart rate in the intervention group was lower than control group, but respiratory rate was higher than the control group (p < 0.05). The traditional analgesia and sedation combined with intracutaneous pyonex reduced the total amount and treatment period of sedative and analgesic drugs in critically ill patients throughout the treatment process, and it also decreased the adverse reactions such as blood pressure drops and respiratory depression.

Comprehensive analysis of miRNA-mRNA/lncRNA during gonadal development of triploid female rainbow trout (Oncorhynchus mykiss).

Chromosomal ploidy manipulation is one of the means to create excellent germplasm. Triploid fish could provide an ideal sterile model for searching of a underlying mechanism of abnormality in meiosis. The complete understanding of the coding and noncoding RNAs regulating sterility caused by meiosis abnormality is still not well understood. By high-throughput sequencing, we compared the expression profiles of gonadal mRNA, long non-coding RNA (lncRNA), and microRNA (miRNA) at three different developmental stages between the diploid (XX) and triploid (XXX) female rainbow trout. These stages were gonads before differentiation (65 days post fertilisation, dpf), at the beginning of morphological differences (180 dpf) and showing clear difference between diploids and triploids (600 dpf), respectively. A majority of differentially expressed (DE) RNAs were identified, and 22 DE mRNAs related to oocyte meiosis and homologous recombination were characterized. The predicted miRNA-mRNA/lncRNA networks of 3 developmental stages were constructed based on the target pairs of DE lncRNA-miRNA and DE mRNA-miRNA. According to the networks, meiosis-related gene of ccne1 was targeted by dre-miR-15a-5p_R + 1, and 6 targeted DE lncRNAs were identified. Also, qRT-PCR was performed to validate the credibility of the network. Overall, this study explored the potential interplay between coding and noncoding RNAs during the gonadal development of polyploid fish. The mRNA, lncRNA and miRNA screened in this study may be helpful to identify the functional elements regulating fertility of rainbow trout, which may provide reference for character improvement in aquaculture.

Yellow nutsedge WRI4-like gene improves drought tolerance in Arabidopsis thaliana by promoting cuticular wax biosynthesis.

BACKGROUND: Cuticular wax plays important role in protecting plants from drought stress. In Arabidopsis WRI4 improves drought tolerance by regulating the biosynthesis of fatty acids and cuticular wax. Cyperus esculentus (yellow nutsedge) is a tough weed found in tropical and temperate zones as well as in cooler regions. In the current study, we report the molecular cloning of a WRI4-like gene from Cyperus esculentus and its functional characterization in Arabidopsis. RESULTS: Using RACE PCR, full-length WRI-like gene was amplified from yellow nutsedge. Phylogenetic analyses and amino acid comparison suggested it to be a WRI4-like gene. According to the tissue-specific expression data, the highest expression of WRI4-like gene was found in leaves, followed by roots and tuber. Transgenic Arabidopsis plants expressing nutsedge WRI4-like gene manifested improved drought stress tolerance. Transgenic lines showed significantly reduced stomatal conductance, transpiration rate, chlorophyll leaching, water loss and improved water use efficiency (WUE). In the absence of drought stress, expression of key genes for fatty acid biosynthesis was not significantly different between transgenic lines and WT while that of cuticular wax biosynthesis genes was significantly higher in transgenic lines than WT. The PEG-simulated drought stress significantly increased expression of key genes for fatty acid as well as wax biosynthesis in transgenic Arabidopsis lines but not in WT plants. Consistent with the gene expression data, cuticular wax load and deposition was significantly higher in stem and leaves of transgenic lines compared with WT under control as well as drought stress conditions. CONCLUSIONS: WRI4-like gene from Cyperus esculentus improves drought tolerance in Arabidopsis probably by promoting cuticular wax biosynthesis and deposition. This in turn lowers chlorophyll leaching, stomatal conductance, transpiration rate, water loss and improves water use efficiency under drought stress conditions. Therefore, CeWRI4-like gene could be a good candidate for improving drought tolerance in crops.

Transcriptomic analysis of Eruca vesicaria subs. sativa lines with contrasting tolerance to polyethylene glycol-simulated drought stress.

BACKGROUND: Eruca vesicaria subsp. sativa is one of the Cruciferae species most tolerant to drought stress. In our previous study some extremely drought-tolerant/sensitive Eruca lines were obtained. However little is known about the mechanism for drought tolerance in Eruca. METHODS: In this study two E. vesicaria subs. sativa lines with contrasting drought tolerance were treated with liquid MS/PEG solution. Total RNA was isolated from 7-day old whole seedlings and then applied to Illumina sequencing platform for high-throughput transcriptional sequencing. RESULTS: KEGG pathway analysis indicated that differentially expressed genes (DEGs) involved in alpha-Linolenic acid metabolism, Tyrosine metabolism, Phenylalanine, Tyrosine and tryptophan biosynthesis, Galactose metabolism, Isoquinoline alkaloid biosynthesis, Tropane, Piperidine and pyridine alkaloid biosynthesis, Mineral absorption, were all up-regulated specifically in drought-tolerant (DT) Eruca line under drought stress, while DEGs involved in ribosome, ribosome biogenesis, Pyrimidine metabolism, RNA degradation, Glyoxylate and dicarboxylate metabolism, Aminoacyl-tRNA biosynthesis, Citrate cycle, Methane metabolism, Carbon fixation in photosynthetic organisms, were all down-regulated. 51 DEGs were found to be most significantly up-regulated (log2 ratio ≥ 8) specifically in the DT line under PEG treatment, including those for ethylene-responsive transcription factors, WRKY and bHLH transcription factors, calmodulin-binding transcription activator, cysteine-rich receptor-like protein kinase, mitogen-activated protein kinase kinase, WD repeat-containing protein, OPDA reductase, allene oxide cyclase, aquaporin, O-acyltransferase WSD1, C-5 sterol desaturase, sugar transporter ERD6-like 12, trehalose-phosphate phosphatase and galactinol synthase 4. Eight of these 51 DEGs wre enriched in 8 COG and 17 KEGG pathways. CONCLUSIONS: DEGs that were found to be most significantly up-regulated specifically in the DT line under PEG treatment, up-regulation of DEGs involved in Arginine and proline metabolism, alpha-linolenic acid metabolism and down-regulation of carbon fixation and protein synthesis might be critical for the drought tolerance in Eruca. These results will be valuable for revealing mechanism of drought tolerance in Eruca and also for genetic engineering to improve drought tolerance in crops.

Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3.

BACKGROUND: Microglial polarization with M1/M2 phenotype shifts and the subsequent neuroinflammatory responses are vital contributing factors for spinal cord injury (SCI)-induced secondary injury. Nuclear factor-κB (NF-κB) is considered the central transcription factor of inflammatory mediators, which plays a crucial role in microglial activation. Lysine acetylation of STAT1 seems necessary for NF-kB pathway activity, as it is regulated by histone deacetylases (HDACs). There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI. We investigated the potential molecular mechanisms that focus on the phenotypic transition of microglia and the STAT1-mediated NF-κB acetylation after a VPA treatment. METHODS: The Basso-Beattie-Bresnahan locomotion scale, the inclined plane test, the blood-spinal cord barrier, and Nissl staining were employed to determine the neuroprotective effects of VPA treatment after SCI. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (INF)-γ was used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of VPA treatment. Immunofluorescent staining and Western blot analysis were used to detect HDAC3 nuclear translocation, activity, and NF-κB signaling pathway activation to evaluate the effects of VPA treatment. The impact of STAT1 acetylation on NF-kB pathway and the interaction between STAT1 and NF-kB were assessed to evaluate anti-inflammation effects of VPA treatment and also whether these effects were dependent on a STAT1/NF-κB pathway to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after SCI. RESULTS: The results showed that the VPA treatment promoted the phenotypic shift of microglia from M1 to M2 phenotype and inhibited microglial activation, thus reducing the SCI-induced inflammatory factors. The VPA treatment upregulation of the acetylation of STAT1/NF-κB pathway was likely caused by the HDAC3 translocation to the nucleus and activity. These results indicated that the treatment with the VPA suppressed the expression and the activity of HDAC3 and enhanced STAT1, as well as NF-κB p65 acetylation following a SCI. The acetylation status of NF-kB p65 and the complex with NF-κB p65 and STAT1 inhibited the NF-kB p65 transcriptional activity and attenuated the microglia-mediated central inflammatory response following SCI. CONCLUSIONS: These results suggested that the VPA treatment attenuated the inflammatory response by modulating microglia polarization through STAT1-mediated acetylation of the NF-κB pathway, dependent of HDAC3 activity. These effects led to neuroprotective effects following SCI.

The Use of Cryotherapy for the Prevention of Wound Complications in the Treatment of Calcaneal Fractures.

We analyzed the risk factors for skin infection and necrosis after calcaneal fracture surgery and evaluated the effect of cryotherapy in preventing postoperative skin infections and necrosis. We studied 129 calcaneal fracture patients (148 feet) who had undergone open reduction and internal fixation from January 2008 to December 2010. Three groups included were: control (44 patients; 49 feet), preoperative cryotherapy (43 patients; 48 feet), and perioperative cryotherapy (42 patients; 51 feet). The wound infection rate, Maryland foot score, and postoperative visual analog scale (VAS) score were compared. Risk factors for infection were analyzed using multinomial logistic regression. Both cryotherapy groups had lower infection rates, higher Maryland foot scores, lower VAS scores, and shorter hospitalizations than the control group (p < .05). The perioperative cryotherapy group had a lower infection rate, higher Maryland foot score, and shorter hospitalization (p < .05) but similar VAS score compared with the preoperative cryotherapy group (p > .05). Pre- and postoperative cryotherapy, postoperative drainage, surgical timing, smoking index, alcoholism, and suture method were risk factors for postoperative infection and necrosis. The risk of these can be largely reduced by patients not smoking and drinking alcohol and surgeons choosing the appropriate surgical timing, improving the suturing method, and performing postoperative drainage. Perioperative cryotherapy might be an effective method to decrease the postoperative infection rate, shorten the hospital stay, and reduce postoperative pain. Our findings require further validation in well-designed randomized controlled trials.

MicroRNA-542-3p inhibits the growth of hepatocellular carcinoma cells by targeting FZD7/Wnt signaling pathway.

MicroRNAs (miRNA) are relevant regulators of the tumorigenesis of various cancers, such as hepatocellular carcinoma (HCC). Recent studies have suggested that miR-542-3p is a tumor suppressor gene in numerous cancers. However, the role of miR-542-3p in HCC remains unclear. This study showed that miR-542-3p was downregulated in HCC tissues and cell lines. MTT, colony formation, and cell cycle assays revealed that miR-542-3p overexpression inhibited HCC cell growth, whereas miR-542-3p suppression promoted cell growth. Frizzled7 (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-542-3p through dual-luciferase reporter assay, RT-qPCR, and Western blot. The mRNA expression of FZD7 was inversely correlated with miR-542-3p expression in HCC tissues. miR-542-3p overexpression could significantly decrease the activation of Wnt signaling pathway in HCC cells. FZD7 overexpression could significantly reverse the inhibitory effect of miR-542-3p on HCC cell growth and Wnt signaling pathway. Taken together, our study suggests that miR-542-3p inhibits HCC cell growth by targeting FZD7 and inhibiting Wnt signaling pathway. The decreased miR-542-3p expression may also contribute to the progression of HCC and may represent a novel molecular therapeutic target for HCC.

Development and Sensing Properties Study of Underwater Assembled Water Depth-Inclination Sensors for a Multi-Component Mooring System, Using a Self-Contained Technique.

Prototype monitoring techniques play an important role in the safety guarantee of mooring systems in marine engineering. In general, the complexities of harsh ocean environmental conditions bring difficulties to the traditional monitoring methods of application, implementation and maintenance. Large amounts of existing mooring systems still lack valid monitoring strategies. In this paper, an underwater monitoring method which may be used to achieve the mechanical responses of a multi-point catenary mooring system, is present. A novel self-contained assembled water depth-inclination (D-I) sensor is designed and manufactured. Several advanced technologies, such as standalone, low power consumption and synchronism, are considered to satisfy the long-term implementation requirements with low cost during the design process. The design scheme of the water resistance barrel and installation clamp, which satisfies the diver installation, are also provided in the paper. An on-site test has previously been carried out on a production semisubmersible platform in the South China Sea. The prototype data analyses, including the D-I value in the time domain (including the data recorded during the mooring retraction and release process) and spectral characteristics, are presented to reveal the accuracy, feasibility and stability of the sensor in terms of fitting for the prototype monitoring of catenary mooring systems, especially for in-service aging platforms.

Drug-Resistant Characteristics, Genetic Diversity, and Transmission Dynamics of Multidrug-Resistant Mycobacterium tuberculosis in Jiangxi, China.

Purpose: In this study, we aimed to determine the transmission pattern of multidrug-resistant tuberculosis (MDR-TB) isolates circulating in Jiangxi Province with whole-genome sequencing (WGS). In addition, we also sought to describe mutational resistome of MDR-TB isolates. Patients and Methods: A total of 115 MDR-TB isolates determined by the phenotypic proportion method of drug susceptibility testing between January 2018 and December 2022 from provincial drug surveillance (DRS) in Jiangxi were included in our analysis. The demographic data and treatment history were extracted from the National TB Registry System. WGS was used to analyze the genotypic characteristics of drug resistance and transmissions. Results: About 62.6% of MDR-TB strains were isolated from cases that received previous anti-tuberculosis treatment. According to the WGS results, 96.5% were genotypic MDR-TB, and more than half of MDR-TB isolates tested were also resistant to streptomycin (59.1%), ethambutol (56.5%), and fluroquinolones (53.0%), while resistance to cycloserine and linezolid was lowest, only in two (1.7%) and one (0.9%) isolate, respectively. Ser450Leu in rpoB (57.9%), Ser315Thr in katG (74.1%), Met306Val in embB (40.0%), Lys43Arg in rpsL (75.0%), Ala90Val in gyrA (32.8%) were predominant mutant types among the rifampin-, isoniazid-, ethambutol-, streptomycin-, fluoroquinolones-resistant isolates, respectively. Lineage 2 (East Asian genotype) occurred at the highest frequency with 97 cases (84.3%), followed by lineage 4 (Euro-American genotype) with 18 cases (15.7%). Additionally, 5 clusters consisting of 10 isolates were identified in the present study, demonstrating a clustering rate of 8.7%. Conclusion: MDR/Rifampicin-Resistant (RR)-TB epidemic in this region is driven by lineage 2 clade that also show higher resistance to other anti-tuberculosis drugs. Lower cluster rates compared with a relatively higher proportion of new MDR-TB cases indicate that a considerable number of MDR-TB cases remain undiagnosed.

Is circulating tumor cell count-driven cost-effective for first-line therapy choice in HR+/HER2- metastatic breast cancer in the United States?

BACKGROUND: Circulating tumor cell (CTC) counting may be a useful non-invasive biomarker that helps patients choose first-line treatment options. Nevertheless, the cost of CTC inspection may impose an economic burden on patients, necessitating the simultaneous consideration of both its clinical effectiveness and cost. We evaluated the cost-effectiveness of CTC count-guided chemotherapy and endocrine therapy as first-line therapy for HR+/HER2-metastatic breast cancer (MBC) from the perspective of US payers. METHODS: Based on the STIC CTC trial, a Markov model was constructed for three health states, and health outcomes were measured in quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to assess the robustness of the incremental cost per QALY. RESULTS: The base-case analysis revealed that CTC count-driven treatment was associated with improved effectiveness by 0.07 QALYs and increased the overall cost by $9187.05 compared with clinician-driven first-line treatment choices, leading to an ICER of $138 354.15 per QALY. One-way sensitivity analysis indicated that the model was most sensitive to the cost of treatment for neutropenia and the utility for PFS; probability sensitivity analysis indicated that CTC count-driven treatment choices would be considered the cost-effective option at a willingness-to-pay threshold of $150 000 per QALY. CONCLUSIONS: The findings of this cost-effectiveness analysis suggest that, at the current price of CTC enumeration, choosing first-line treatment options based on CTC count is a cost-effectiveness approach for treating patients with HR+/HER2- MBC in the US.

A meta-analysis of the impact of pharmacist interventions on clinical outcomes in patients with type-2 diabetes.

OBJECTIVE: To evaluate the effects of pharmacist interventions in type-2 diabetes patients by collecting and evaluating literature. METHODS: A systematic search was conducted across six databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Cochrane Library, from January 2001 to January 2023. Randomized controlled trials evaluating the clinical outcomes of pharmacist interventions on type-2 diabetes patients were searched, and data were extracted and analysed by RevMan version 5.4 software. RESULTS: A total of 35 studies involving 4827 patients were included. Meta-analysis demonstrated that pharmacist interventions had an influence on improving patients' HbA1c (MD=-0.70), LDL-C (MD=-5.51), SBP (MD=-4.58), DBP (MD=-1.90], BMI (MD=-0.47) and FBG (MD=-19.82), but there was no evidence from the study that pharmacist interventions could significantly improve HDL-C (MD=-0.61), TC (MD=-5.12) or TG (MD=-3.14). In addition, medication adherence was significantly improved. CONCLUSION: Pharmacist interventions significantly improved HbA1c, BP, and LDL-C control levels, BMI, and medication adherence in type-2 diabetes patients, but there was no evidence from this study that pharmacist interventions significantly improved HDL-C, TC, or TG. PRACTICE IMPLICATIONS: Effective pharmacist interventions are important to improve type-2 diabetes patients' clinical outcomes.

Constructing magnetic/dielectric dual loss and phonon/electron thermal carriers γ-Al2O3-based yolk-shell microspheres to collaboratively advance microwave absorption and heat conduction.

The severe electromagnetic (EM) interference and overheating issues in 5G/6G electric devices increasingly heighten the need for developing multifunctional materials with large heat conduction (HC) and high EM wave (EMW) absorption. Here, a series of γ-Al2O3-based yolk-shell microspheres (γ-AlOOH, γ-Al2O3, γ-Al2O3@C, γ-Al2O3@Fe3O4@C, and γ-Al2O3@FeAl2O4@Fe@C YSMSs) as multifunctional fillers are investigated for the simultaneous improvement in the HC and EMW absorption of γ-Al2O3-based composites. Using γ-AlOOH YSMSs as precursors produced from a hydrothermal method, the γ-Al2O3-based YSMSs were synthesized via an annealing route or soaking-annealing route; their phases, textures, and compositions were finely adjusted by changing the Al3+/Fe3+ molar ratio (ß) and annealing temperature (Ta). Results show that the thermal transfers in the γ-Al2O3-based YSMSs are promoted by the synergic effect of phonons and electrons when they are utilized as thermally conductive fillers. Comparatively, the γ-Al2O3@FeAl2O4@Fe@C YSMSs formed at ß = 8 : 2 and Ta = 700 °C exhibit a high HC of 1.84-3.29 W m-1 K-1 in a loading amount of 5-40%, exceeding those of not merely γ-Al2O3, γ-AlOOH, γ-Al2O3@C, and γ-Al2O3@Fe3O4@C YSMSs but also most previously reported fillers. Furthermore, the γ-Al2O3@Fe3O4@C YSMSs exhibit prominent EMW absorption properties with a large ABW/d of 4.49 GHz mm-1 (just 30% loading), superior to most other Al2O3-based absorbers. Such excellent EMW absorption could be explained by magnetic/dielectric dual loss and significant cavity and interfacial effects caused by yolk-shell structures. In conclusion, this work inspires the development of yolk-shell structures with magnetic/dielectric dual loss and phonon/electron thermal carriers as high-performance bifunctional materials with exceptional heat conduction and EMW absorption.

Transforming Natural Eggshell and Diatomite into Bioactive Calcium Silicate Material for Bone Regeneration.

Calcium silicate (CS), a new and important bioceramic bone graft material, is prepared by using eggshells, which have a porous structure and are rich in calcium ions. Furthermore, the preparation of new CS materials using eggshells and diatomaceous earth minimizes their negative impact on the environment. In this study, we prepared CS materials using a high-temperature calcination method. The composition of the material was demonstrated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) analysis confirmed the porous structure of the CS material. We also introduced ZnO to prepare ZnO-CS with antibacterial properties and showed that ZnO-CS exhibits excellent antibacterial effects through in vitro antibacterial experiments. Subsequent in vitro mineralization experiments demonstrated that ZnO-CS promoted the formation of a hydroxyapatite layer. Furthermore, in vitro cytotoxicity experiments demonstrated that ZnO-CS had very good biosafety and promoted cell proliferation. These findings were confirmed through subsequent cell proliferation experiments. Our results indicate that the novel ZnO-CS is a promising candidate for bone tissue engineering.