The BTB-BACK-TAZ domain protein MdBT2 reduces drought resistance by weakening the positive regulatory effect of MdHDZ27 on apple drought tolerance via ubiquitination.

Drought stress is one of the dominating challenges to the growth and productivity in crop plants. Elucidating the molecular mechanisms of plants responses to drought stress is fundamental to improve fruit quality. However, such molecular mechanisms are poorly understood in apple (Malus domestica Borkh.). In this study, we explored that the BTB-BACK-TAZ protein, MdBT2, negatively modulates the drought tolerance of apple plantlets. Moreover, we identified a novel Homeodomain-leucine zipper (HD-Zip) transcription factor, MdHDZ27, using a yeast two-hybrid (Y2H) screen with MdBT2 as the bait. Overexpression of MdHDZ27 in apple plantlets, calli, and tomato plantlets enhanced their drought tolerance by promoting the expression of drought tolerance-related genes [responsive to dehydration 29A (MdRD29A) and MdRD29B]. Biochemical analyses demonstrated that MdHDZ27 directly binds to and activates the promoters of MdRD29A and MdRD29B. Furthermore, in vitro and in vivo assays indicate that MdBT2 interacts with and ubiquitinates MdHDZ27, via the ubiquitin/26S proteasome pathway. This ubiquitination results in the degradation of MdHDZ27 and weakens the transcriptional activation of MdHDZ27 on MdRD29A and MdRD29B. Finally, a series of transgenic analyses in apple plantlets further clarified the role of the relationship between MdBT2 and MdHDZ27, as well as the effect of their interaction on drought resistance in apple plantlets. Collectively, our findings reveal a novel mechanism by which the MdBT2-MdHDZ27 regulatory module controls drought tolerance, which is of great significance for enhancing the drought resistance of apple and other plants.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

Barriers and facilitators in implementing early essential newborn care of well-born babies in low- and middle-income countries: A mixed-method systematic review.

BACKGROUND: Evidences have demonstrated the effectiveness of early essential newborn care. However, the implementation of early essential newborn care is suboptimal. The aim is to identify and synthesise the barriers and facilitators impacting the implementation of early essential newborn care in low- and middle-income countries. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, CINAHL, CNKI, Wan Fang Data, SinoMed and Google Scholar. METHODS: Two authors independently screened, performed quality assessment using the Mixed Methods Appraisal Tool and extracted data. This review includes papers that reported the barriers and facilitators of implementing early essential newborn care in low- and middle-income countries from the view of healthcare providers. Barriers and facilitators were coded according to the consolidated framework for implementation research in a deductive way and then been inducted into five common themes. This review followed synthesis without meta-analysis reporting guideline. RESULTS: A total of 28 studies were included. Five inductive common themes influencing implementing early essential newborn care in low- and middle-income countries were system-level healthcare factors, healthcare providers' knowledge and beliefs, the requirements of mothers or families, adapting to routine practice and the working climate of organisation. CONCLUSION: The factors were from system level, facility level and individual level and were inducted into five themes. Based on this review, decision-makers could tailor implementing strategies to narrow the gap between the evidence and implementation. RELEVANCE TO CLINICAL PRACTICE: The study offers guidance for health professionals to identify barriers and facilitators in implementing early essential newborn care and make tailored strategies when implementing early essential newborn care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contributions.

Ethylene inhibits malate accumulation in apple by transcriptional repression of aluminum-activated malate transporter 9 via the WRKY31-ERF72 network.

Malic acid accumulation in the vacuole largely determines acidity and perception of sweetness of apple. It has long been observed that reduction in malate level is associated with increase in ethylene production during the ripening process of climacteric fruits, but the molecular mechanism linking ethylene to malate reduction is unclear. Here, we show that ethylene-modulated WRKY transcription factor 31 (WRKY31)-Ethylene Response Factor 72 (ERF72)-ALUMINUM ACTIVATED MALATE TRANSPORTER 9 (Ma1) network regulates malate accumulation in apple fruit. ERF72 binds to the promoter of ALMT9, a key tonoplast transporter for malate accumulation of apple, transcriptionally repressing ALMT9 expression in response to ethylene. WRKY31 interacts with ERF72, suppressing its transcriptional inhibition activity on ALMT9. In addition, WRKY31 directly binds to the promoters of ERF72 and ALMT9, transcriptionally repressing and activating ERF72 and ALMT9, respectively. The expression of WRKY31 decreases in response to ethylene, lowering the transcription of ALMT9 directly and via its interactions with ERF72. These findings reveal that the regulatory complex WRKY31 forms with ERF72 responds to ethylene, linking the ethylene signal to ALMT9 expression in reducing malate transport into the vacuole during fruit ripening.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Retrieval of Trophoblast Cells from the Cervical Canal: A Promising Non-invasive Method for Prenatal Diagnosis.

Background: Extravillous trophoblasts (EVTs) cells have shown promise for their application in non-invasive prenatal diagnosis during the first trimester. The Trophoblast Retrieval and Isolation from the Cervix (TRIC) method allows for the isolation of homogeneous trophoblast cells from pregnant women as early as 5 weeks gestation. Objective: This study aimed to explore the potential value of extravillous trophoblast cells collected from the cervix, enriched, and purified using the TRIC method for first-trimester prenatal diagnosis. Methods: A prospective observational study was conducted, and we collected extravillous trophoblast cells from the cervixes of 100 pregnant women between 5-7 weeks gestation before an induced abortion. Subsequently, these cells underwent STR analysis and fluorescence in situ hybridization (FISH). Results: Out of the 100 cases, trophoblast cells were successfully collected from 96 cases. Among them, STR analysis revealed maternal cell contamination in 13 cases. Gender determination using FISH showed 44 male cases (including one case with 47, XY, +21) and 39 female cases (including one case with 47, XXX). The results of the FISH examination of these 83 cases were in concordance with those of the villi FISH examination. Conclusions: The collection of fetal trophoblast cells from the cervix represents a feasible and non-invasive approach for first-trimester prenatal diagnosis. The TRIC method enables efficient enrichment and purification of trophoblast cells, which can be of significant benefit for subsequent diagnosis using the FISH method.

MdbHLH3 modulates apple soluble sugar content by activating phosphofructokinase gene expression.

Sugars are involved in plant growth, fruit quality, and signaling perception. Therefore, understanding the mechanisms involved in soluble sugar accumulation is essential to understand fruit development. Here, we report that MdPFPß, a pyrophosphate-dependent phosphofructokinase gene, regulates soluble sugar accumulation by enhancing the photosynthetic performance and sugar-metabolizing enzyme activities in apple (Malus domestica Borkh.). Biochemical analysis revealed that a basic helix-loop-helix (bHLH) transcription factor, MdbHLH3, binds to the MdPFPß promoter and activates its expression, thus promoting soluble sugar accumulation in apple fruit. In addition, MdPFPß overexpression in tomato influenced photosynthesis and carbon metabolism in the plant. Furthermore, we determined that MdbHLH3 increases photosynthetic rates and soluble sugar accumulation in apple by activating MdPFPß expression. Our results thus shed light on the mechanism of soluble sugar accumulation in apple leaves and fruit: MdbHLH3 regulates soluble sugar accumulation by activating MdPFPß gene expression and coordinating carbohydrate allocation.

A study of multinucleated giant cells in esophageal cancer.

OBJECTIVES: To evaluate the occurrence, abundance, distribution, nature and clinical significance of multinucleated giant cell (MGC) in esophageal cancer. MATERIALS AND METHODS: MGCs were examined with conventional pathology, immunohistochemistry and immunofluorescence in 107 esophageal cancer tissues. The findings were correlated to pathological diagnosis and clinical behavior of the cancers. RESULTS: MGCs were identified in 31.7% (34/107) of the cases. MGCs were positive for CD11c, CD11b, CD32, CD16, HLA-DR and MMP9, and negative for CD163, CD206 and CD64 giving a molecular profile of proinflammatory M1 but not immunosuppressive M2. MGCs were significantly related to decreased lymph node metastasis (p = 0.011), low pTNM stage (p = 0.044), favorable survival (p = 0.04), squamous cell cancer type rather than other histopathological subtypes (p = 0.020) and associated to better differentiation (p = 0.063). CONCLUSIONS: MGCs belong to M1 macrophage and perform phagocytosis and scavenging of cancer cells that would benefit patients' survival and could serve as a prognostic marker.

The apple bHLH transcription factor MdbHLH3 functions in determining the fruit carbohydrates and malate.

Changes in carbohydrates and organic acids largely determine the palatability of edible tissues of horticulture crops. Elucidating the potential molecular mechanisms involved in the change in carbohydrates and organic acids, and their temporal and spatial crosstalk are key steps in understanding fruit developmental processes. Here, we used apple (Malus domestica Borkh.) as research materials and found that MdbHLH3, a basic helix-loop-helix transcription factor (bHLH TF), modulates the accumulation of malate and carbohydrates. Biochemical analyses demonstrated that MdbHLH3 directly binds to the promoter of MdcyMDH that encodes an apple cytosolic NAD-dependent malate dehydrogenase, activating its transcriptional expression, thereby promoting malate accumulation in apple fruits. Additionally, MdbHLH3 overexpression increased the photosynthetic capacity and carbohydrate levels in apple leaves and also enhanced the carbohydrate accumulation in fruits by adjusting carbohydrate allocation from sources to sinks. Overall, our findings provide new insights into the mechanism of how the bHLH TF MdbHLH3 modulates the fruit quality. It directly regulates the expression of cytosolic malate dehydrogenase MdcyMDH to coordinate carbohydrate allocation and malate accumulation in apple.

BTB-TAZ Domain Protein MdBT2 Modulates Malate Accumulation and Vacuolar Acidification in Response to Nitrate.

Excessive application of nitrate, an essential macronutrient and a signal regulating diverse physiological processes, decreases malate accumulation in apple (Malus domestica) fruit, but the underlying mechanism remains poorly understood. Here, we show that an apple BTB/TAZ protein, MdBT2, is involved in regulating malate accumulation and vacuolar pH in response to nitrate. In vitro and in vivo assays indicate that MdBT2 interacts directly with and ubiquitinates a bHLH transcription factor, MdCIbHLH1, via the ubiquitin/26S proteasome pathway in response to nitrate. This ubiquitination results in the degradation of MdCIbHLH1 protein and reduces the transcription of MdCIbHLH1-targeted genes involved in malate accumulation and vacuolar acidification, including MdVHA-A, which encodes a vacuolar H+-ATPase, and MdVHP1, which encodes a vacuolar H+-pyrophosphatase, as well as MdALMT9, which encodes an aluminum-activated malate transporter. A series of transgenic analyses in apple materials including fruits, plantlets, and calli demonstrate that MdBT2 controls nitrate-mediated malate accumulation and vacuolar pH at least partially, if not completely, via regulating the MdCIbHLH1 protein level. Taken together, these findings reveal that MdBT2 regulates the stability of MdCIbHLH1 via ubiquitination in response to nitrate, which in succession transcriptionally reduces the expression of malate-associated genes, thereby controlling malate accumulation and vacuolar acidification in apples under high nitrate supply.

The regulatory module MdPUB29-MdbHLH3 connects ethylene biosynthesis with fruit quality in apple.

The plant hormone ethylene is critical for climacteric fruit ripening, while glucose and anthocyanins determine the fruit quality of climacteric fruits such as apple. Understanding the exact molecular mechanism for this process is important for elucidating the interconnection of ethylene and fruit quality. Overexpression of apple MdbHLH3 gene, an anthocyanin-related basic helix-loop-helix transcription factor (bHLH TF) gene, promotes ethylene production, and transgenic apple plantlets and trees exhibit ethylene-related root developmental abnormalities, premature leaf senescence, and fruit ripening. Biochemical analyses demonstrate that MdbHLH3 binds to the promoters of three genes that are involved in ethylene biosynthesis, including MdACO1, MdACS1, and MdACS5A, activating their transcriptional expression, thereby promoting ethylene biosynthesis. High glucose-inhibited U-box-type E3 ubiquitin ligase MdPUB29, the ortholog of Arabidopsis AtPUB29 in apple, influences the expression of ethylene biosynthetic genes and ethylene production by direct ubiquitination of the MdbHLH3 protein. Our findings provide new insights into the ubiquitination of MdbHLH3 by glucose-inhibited ubiquitin E3 ligase MdPUB29 in the regulation of ethylene biosynthesis as well as indicate that the regulatory module MdPUB29-MdbHLH3 connects ethylene biosynthesis with fruit quality in apple.

Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple.

Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants.

Effect of CLIC1 gene silencing on proliferation, migration, invasion and apoptosis of human gallbladder cancer cells.

This study aimed to explore the effects of CLIC1 gene silencing on proliferation, migration, invasion and apoptosis of human gallbladder cancer (GBC). GBC and normal gallbladder tissues were extracted for the detection of mRNA and protein expressions of CLIC1. GBC-SD and NOZ cells in the logarithmic growth phase were selected to conduct the experiment. Three different siRNA recombined expression vectors were established using CLIC1 as a target at different sites. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were, respectively, used to detect the CLIC1 mRNA and protein expressions. MTT assay was performed to detect the cell proliferation. Flow cytometry was applied to measure the cell apoptosis and cell cycle distribution. The variations of cell migration and invasion were evaluated using Transwell assay. GBC tissues showed higher CLIC1 mRNA and protein expressions than normal gallbladder tissues. The CLIC1 mRNA and protein expressions in the CLIC1 siRNA group were significantly lower than those in the NC and blank groups. Compared with the NC and blank groups, the CLIC1 siRNA group showed a significant decrease in cell proliferation but an obvious increase in apoptosis rate in GBC cells. Besides, in the CLIC1 siRNA group, cell percentage in G0/G1 and G2/M phase was gradually increased but decreased in S phases. The migration and invasion abilities in GBC cells were significantly lower than those in the NC and blank groups. Our study demonstrates that CLIC1 gene silencing could promote apoptosis and inhibit proliferation migration and invasion of GBC cells.

The R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple.

Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate-metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple.

Ectopic expression of the apple nucleus-encoded thylakoid protein MdY3IP1 triggers early-flowering and enhanced salt-tolerance in Arabidopsis thaliana.

BACKGROUND: The roles in photosystem I (PSI) assembly of the nucleus-encoded thylakoid protein Y3IP1 who interacts with the plastid-encoded Ycf3 protein that has been well-characterized in plants. However, its function and potential mechanisms in other aspects remain poorly understood. RESULTS: We identified the apple MdY3IP1 gene, which encodes a protein highly homologous to the Arabidopsis Y3IP1 (AtY3IP1). Ectopic expression of MdY3IP1 triggered early-flowering and enhanced salt tolerance in Arabidopsis plants. MdY3IP1 controlled floral transition by accelerating sugar metabolism process in plant cells, thereby influencing the expression of flowering-associated genes. The increase in salt stress tolerance in MdY3IP1-expressing plants correlated with reduced reactive oxygen species (ROS) accumulation, and an increase in lateral root development by regulating both auxin biosynthesis and transport, as followed by enhancement of salt tolerance in Arabidopsis. Overall, these findings provide new evidences for additional functions of Y3IP1-like proteins and their underlying mechanisms of which Y3IP1 confers early-flowering and salt tolerance phenotypes in plants. CONCLUSIONS: These observations suggest that plant growth and stress resistance can be affected by the regulation of the MdY3IP1 gene. Further molecular and genetic approaches will accelerate our knowledge of MdY3IP1 functions in PSI complex formation and plants stress resistance, and inform strategies for creating transgenic crop varieties with early maturity and high-resistant to adverse environmental conditions.

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy.

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

The long noncoding RNA, EGFR-AS1, a target of GHR, increases the expression of EGFR in hepatocellular carcinoma.

LncRNA has provided an important new perspective regarding gene regulation. Both the expression and activation of EGFR have been proven to be under the tight control of the GHR pathway. EGFR-AS1 has been found to inhibit the expression of EGFR. GHR-siRNA and EGFR-AS1-siRNA were transfected into HCC cell lines, and a series of WB, q-PCR, and IF experiments was conducted to evaluate whether EGFR-AS1 participated in the regulation of GHR and EGFR. We found that impeded expression of GHR decreased the expression of EGFR and EGFR-AS1 in vivo and in vitro. Then, it was verified that EGFR and EGFR-AS1 were relatively upregulated in HCC tissue, and they were significantly related to some clinical characteristics and patient prognosis. Furthermore, EGFR-AS1 was determined to promote HCC development by improving the ability of invasion and proliferation of HCC cells in vitro, and it was also found to affect the cell cycle. Our study identified that EGFR-AS1 may promote HCC genesis and development. EGFR-AS1 may act as a prognostic factor in HCC. More importantly, we observed that the inhibition of EGFR-AS1 in HCC cells significantly impeded cell proliferation and invasion in vivo, which might provide a potential possibility for targeted therapy of HCC.

An Electronic Adherence Measurement Intervention to Reduce Clinical Inertia in the Treatment of Uncontrolled Hypertension: The MATCH Cluster Randomized Clinical Trial.

BACKGROUND: To appropriately manage uncontrolled hypertension, clinicians must decide whether blood pressure (BP) is above goal due to a need for additional medication or to medication nonadherence. Yet, clinicians are poor judges of adherence, and uncertainty about adherence may promote inertia with respect to medication modification. OBJECTIVE: We aimed to determine the effect of sharing electronically-measured adherence data with clinicians on the management of uncontrolled hypertension. DESIGN: This was a cluster randomized trial. PARTICIPANTS: Twenty-four primary care providers (12 intervention, 12 usual care; cluster units) and 100 patients with uncontrolled hypertension (65 intervention, 35 usual care) were included in the study. INTERVENTIONS: At one visit per patient, clinicians in the intervention group received a report summarizing electronically measured adherence to the BP regimen and recommended clinical actions. Clinicians in the control group did not receive a report. MAIN MEASURES: The primary outcome was the proportion of visits with appropriate clinical management (i.e., treatment intensification among adherent patients and adherence counseling among nonadherent patients). Secondary outcomes included patient-rated quality of care and communication during the visit. KEY RESULTS: The proportion of visits with appropriate clinical management was higher in the intervention group than the control group (45 out of 65; 69 %) versus (12 out of 35; 34 %; p = 0.001). A higher proportion of adherent patients in the intervention group had their regimen intensified (p = 0.01), and a higher proportion of nonadherent patients in the intervention group received adherence counseling (p = 0.005). Patients in the intervention group were more likely to give their clinician high ratings on quality of care (p = 0.05), and on measures of patient-centered (p = 0.001) and collaborative communication (p = 0.02). CONCLUSIONS: Providing clinicians with electronically-measured antihypertensive adherence reports reduces inertia in the management of uncontrolled hypertension. TRIAL REGISTRATION: NCT01257347 ; http://clinicaltrials.gov/show/ NCT01257347.

Comparison of peripheral iridectomy methods for posterior chamber phakic intraocular lens implantation in patients with brown irides.

BACKGROUND: We explore and compare the advantages and disadvantages of different operating methods for a peripheral iridectomy (PI) for phakic posterior chamber implantable contact lens (ICL) implantation in patients with dark-brown irides. METHODS: Forty-six patients completed this prospective comparative study. Neodymium: yttrium-aluminum-garnet (Nd:YAG) PI was performed in 15 patients (30 eyes) 2 weeks prior to surgery (YAG PI group). Surgical PI was performed in 17 patients (34 eyes) 2 weeks prior to the ICL implantation (preoperative PI group), and intraoperative PI was performed during ICL implantation in 14 patients (28 eyes) (intraoperative PI group). The postoperative recovery of visual acuity, intraoperative complications, operation duration, and patients' visual disturbances were compared. RESULTS: Compared with the preoperative BCVA, the uncorrected visual acuity (UCVA) at 1 week was markedly restored in the preoperative PI group (P = 0.004). UCVA in the three groups of patients had all recovered well at 1 and 3 months after ICL implantation and were significantly better than the preoperative BCVA (all P < 0.01). In the YAG PI group, iris bleeding occurred in nine eyes (30.0 %) and 14 eyes (46.7 %) had pigment dispersion; these values were significantly higher than those in the preoperative PI group (5.9 and 14.7 %, respectively, both P = 0.01). In the intraoperative PI group, elevated high intraocular pressure occurred in four eyes (14.3 %), and eight eyes (28.6 %) had varying degrees of pigment dispersion after ICL implantation. CONCLUSIONS: For patients with dark-brown irides, surgical PI performed 2 weeks prior to the implantation facilitated better postoperative recovery of visual acuity. TRIAL REGISTRATION: Current Controlled Trials ISRCTN35178162 . Retrospectively registered March 4th, 2013.

A novel mechanism of resveratrol alleviates Toxoplasma gondii infection-induced pulmonary inflammation via inhibiting inflammasome activation.

BACKGROUND: Infection by Toxoplasma gondii can lead to severe pneumonia, with current treatments being highly inadequate. The NLRP3 inflammasome is one member of the NOD-like receptor family with a pyrin domain, which is crucial in the innate immune defense against T. gondii. Research has shown that resveratrol (RSV) prevents lung damage caused by this infection by inhibiting the T. gondii-derived heat shock protein 70/TLR4/NF-κB pathway, thus reducing the macrophage-driven inflammatory response. However, it should be mentioned that the participation of NLRP3 inflammasome in the immune response to the lung injuries caused by T. gondii infections is not entirely clear. PURPOSE: This study aims to clarify how RSV ameliorates lung damage triggered by Toxoplasma gondii infection, with a particular focus on the pathway involving TLR4, NF-κB, and the NLRP3 inflammasome. METHODS: Both in vitro and in vivo models of infection were developed by employing the RH strain of T. gondii in BALB/c mice and RAW 264.7 macrophage cell lines. The action mechanism of RSV was explored using techniques such as molecular docking, surface plasmon resonance, ELISA, Western blot, co-immunoprecipitation, and immunofluorescence staining. RESULTS: Findings indicate that the suppression of TLR4 or NF-κB impacts the levels of proteins associated with the NLRP3 inflammasome pathway. Additionally, a significant affinity for binding between RSV and NLRP3 was observed. Treatment with RSV led to a marked reduction in the activation and formation of the NLRP3 inflammasome within lung tissues and RAW 264.7 cells, alongside a decrease in IL-1ß concentrations in the bronchoalveolar lavage fluid. These outcomes align with those seen when using the NLRP3 inhibitor CY-09. Moreover, the application of CY-09 prior to RSV negated the latter's anti-inflammatory properties. CONCLUSION: Considering insights from previous research alongside the outcomes of the current investigation, it appears that the TLR4/NF-κB/NLRP3 signaling pathway emerges as a promising target for immunomodulation to alleviate lung injury from T. gondii infection. The evidence gathered in this study lays the groundwork for the continued exploration and potential future clinical deployment of RSV as a therapeutic agent with anti-Toxoplasma properties and the capability to modulate the inflammatory response.