The FKBP (FK506-binding protein) gene family is an important member of the PPlase protease family and plays a vital role during the processes of plant growth and development. However, no studies of ...the FKBP gene family have been reported in cucumber. In this study, 19 FKBP genes were identified in cucumber, which were located on chromosomes 1, 3, 4, 6, and 7. Phylogenetic analysis divided the cucumber FKBP genes into three subgroups. The FKBP genes in the same subgroup exhibited similar structures and conserved motifs. The cis-acting elements analysis revealed that the promoters of cucumber FKBP genes contained hormone-, stress-, and development-related cis-acting elements. Synteny analysis of the FKBP genes among cucumber, Arabidopsis, and rice showed that 12 kinds of syntenic relationships were detected between cucumber and Arabidopsis FKBP genes, and 3 kinds of syntenic relationships were observed between cucumber and rice FKBP genes. The tissue-specific expression analysis showed that some FKBP genes were expressed in all tissues, while others were only highly expressed in part of the 10 types of tissues. The expression profile analysis of cucumber FKBP genes under 13 types of stresses showed that the CsaV3_1G007080 gene was differentially expressed under abiotic stresses (high temperature, NaCl, silicon, and photoperiod) and biotic stresses (downy mildew, green mottle mosaic virus, Fusarium wilt, phytophthora capsica, angular leaf spot, and root-knot nematode), which indicated that the CsaV3_1G007080 gene plays an important role in the growth and development of cucumber. The interaction protein analysis showed that most of the proteins in the FKBP gene family interacted with each other. The results of this study will lay the foundation for further research on the molecular biological functions of the cucumber FKBP gene family.
Objectives. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal ...polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear.Methods. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays.Results. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression.Conclusion. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
The protein phosphatase PP2C plays an important role in plant responses to stress. Therefore, the identification of maize
genes that respond to drought stress is particularly important for the ...improvement and creation of new drought-resistant assortments of maize. In this study, we identified 102
genes in maize at the genome-wide level. We analyzed the physicochemical properties of 102
and constructed a phylogenetic tree with
. By analyzing the gene structure, conserved protein motifs, and synteny, the
were found to be strongly conserved during evolution. Sixteen core genes involved in drought stress and rewatering were screened using gene co-expression network mapping and expression profiling. The qRT-PCR results showed 16 genes were induced by abscisic acid (ABA), drought, and NaCl treatments. Notably,
exhibited a substantial expression difference. Through genetic transformation, we overexpressed
and generated the CRISPR/Cas9 knockout maize mutant
. Overexpressing
in
under drought stress enhanced growth and survival compared with WT plants. The leaves exhibited heightened superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) activities, elevated proline (Pro) content, and reduced malondialdehyde (MDA) content. Conversely,
mutant plants displayed severe leaf dryness, curling, and wilting under drought stress. Their leaf activities of SOD, POD, APX, and CAT were lower than those in B104, while MDA was higher. This suggests that
positively regulates drought tolerance in maize by affecting the antioxidant enzyme activity and osmoregulatory substance content. Subcellular localization revealed that
was localized in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments demonstrated
's interaction with ZmWIN1, ZmADT2, ZmsodC, Zmcab, and ZmLHC2. These findings establish a foundation for understanding maize
gene functions, offering genetic resources and insights for molecular design breeding for drought tolerance.
Abstract
Background
Enhanced recovery following total knee arthroplasty (TKA) has been advocated to enhance postoperative recovery. Multimodal cocktail periarticular injection (MCPI) use for pain ...control in TKA has gained wide acceptance. MCPI-containing corticosteroids are believed to be an effective solution owing to their local anti-inflammatory effects and ability to reduce the local stress response postoperatively. However, there is conflicting evidence regarding its benefits. This trial aims to compare MCPI with a high dose of corticosteroid, normal dose of corticosteroid, and non-corticosteroid during TKA, to assess the effectiveness of MCPI containing corticosteroids in postoperative pain relief, functional improvement, rescue analgesia, and side effects and provide evidence that high-dose corticosteroids result in prolonged pain control and better recovery following TKA.
Methods
This is a double-blinded, randomized, placebo-controlled study. A total of 234 patients scheduled for TKA will be recruited. During surgery, before wound closure, 80 ml of the cocktail analgesic will be injected into the muscle and joint capsule for local infiltration analgesia; the participants will be randomly assigned to three groups to receive a high dose of betamethasone MCPI (group H), normal dose of betamethasone MCPI (group N), and non-betamethasone MCPI (group C). The following indices will be recorded and analyzed: the strongest knee pain experienced during 90° flexion at 6 h, 24 h, 48 h, 72 h, 5 days, 14 days, and 30 days after surgery; 1 min walking ability; and circumference around the patella at 2, 5, 14, and 30 days after surgery; Knee Society knee score at 14 days and 30 days after surgery; C-reactive protein and blood sedimentation; blood sugar 2, 5, 14, and 30 days following surgery; rescue analgesic consumption; and adverse events. If any participant withdraws from the trial, an intention-to-treat analysis will be performed.
Discussion
The results of this study will provide clinical evidence on the effectiveness of MCPI-containing corticosteroids in postoperative pain relief, functional improvement, rescue analgesia, and adverse events, as well as provide evidence on the efficacy of high-dose corticosteroids in prolonged pain control and better recovery following TKA.
Trial registration
Chinese Clinical Trial Registry,
ChiCTR2000038671
. Registered on September 27, 2020.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective To observe the effect of brain exercise training on cognitive function and behavioral and psychological symptoms of patients with mild cognitive impairment （MCI）. Methods 80 patients with ...MCI were randomly divided into the intervention （n = 40） and control groups （n = 40）. In the intervention group， brain exercise training was delivered for 45-60 min twice a week for 12 consecutive weeks. Mini-Mental State Examination Scale （MMSE）， Montreal Cognitive Assessment （MoCA）， Zung’s Self-rating Anxiety Scale （SAS）， Zung’s Self-rating Depression Scale （SDS）， Neuropsychiatric Inventory （NPI） and Pittsburgh Sleep Quality Index （PSQI） between two groups were evaluated at the baseline， 3 months and 6 months， respectively. Results In the control group， the total MMSE scores at 3 and 6 months were significantly declined compared with the baseline value （P < 0.001， P = 0.007）， the scores of attention and calculation domains were significantly decreased （P < 0.001， P = 0.009）， and the score of language domain was a
Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease leading to biliary fibrosis and cirrhosis. Cilofexor is a nonsteroidal farnesoid X receptor agonist that demonstrated ...significant improvements in liver biochemistry and markers of cholestasis in patients with PSC in a phase 2 study. We describe here the rationale, design, and implementation of the phase 3 PRIMIS trial, the largest placebo-controlled trial in PSC.
Adults with large-duct PSC without cirrhosis are randomized 2:1 to receive oral cilofexor 100 mg once daily or placebo for up to 96 weeks during the blinded phase. Patients completing the blinded phase are eligible to receive open-label cilofexor 100 mg daily for up to 96 weeks. The primary objective is to evaluate whether cilofexor reduces the risk of fibrosis progression compared with placebo. Liver biopsy is performed at screening and Week 96 of the blinded phase for histologic assessment of fibrosis. The primary endpoint-chosen in conjunction with guidance from the U.S. Food and Drug Administration-is the proportion of patients with ≥ 1-stage increase in fibrosis according to Ludwig histologic classification at week 96. Secondary objectives include evaluation of changes in liver biochemistry, serum bile acids, liver fibrosis assessed by noninvasive methods, health-related quality of life, and safety of cilofexor.
The phase 3 PRIMIS study is the largest randomized, double-blind, placebo-controlled trial in PSC to date and will allow for robust evaluation of the efficacy and safety of cilofexor in noncirrhotic patients with large-duct PSC.
ClinicalTrials.gov NCT03890120; registered 26/03/2019.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives. To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal ...metastases. Methods. A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3+, CD4+, CD8+, and NK cells were detected by BD FACSCalibur flow cytometer. Results. There was no significant difference in clinical data between the two groups (P>0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P<0.05), OS was significantly longer than that in the control group (P<0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P<0.05), but there was no significant difference in peripheral blood CD3+, CD4+, and CD4+/CD8+ ratio or count of NK cells before and after treatment (P>0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P>0.05). After treatment, peripheral blood CD3+, CD4+, and CD4+/CD8+ ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P<0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P<0.05). Conclusion. The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper presents challenges in an ongoing project related to the design of a premium efficiency three-phase line start permanent magnet synchronous motor (LSPMSM) and proposes an exclusive ...solution through development of a novel magnetic circuit model. Since the LSPMSM is rapidly replacing the conventional induction motors in industrial applications such as pumps, fans and conveyors which require the machine to operate under both frequent start-stop and steady-state conditions for a wide range of time, a trade-off has to be reached between their starting performance and efficiency post-synchronization. Until now this has only been possible with time consuming FEA based design methodology. Hence, understanding the need and scanty availability of literature on simplistic and yet precise magnetic circuit based design of three-phase LSPMSM, this manuscript proposes exclusively a novel magnetic circuit model to design LSPMSM with improved starting performance. Firstly, the aforementioned design issues have been illustrated using different machine configurations developed. Further, a detailed procedure to deal with the design issues with the help of the developed magnetic circuit model is discussed and validated by developing a machine where the trade-off has been reached.
The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, ...some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength.
This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention.
Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR.
ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The equipment monitoring brought by the smart grid big data is difficult to effectively supervise the operation status of the whole network substation, and the typical defects (familial defects) are ...difficult to classify and locate. This paper proposes the substation operation state evaluation algorithm and typical defect classification algorithm. The operating state evaluation algorithm of the substation is based on different operation data generated by the substation. By normalizing the data of different dimensions, the substation is divided into different operating state levels. The typical defect classification algorithm establishes and maintains the historical experience database, and calculates the conditional probability of each information item to realize the correlation between the signal and the defect, and finally judge whether the signal is from a typical defect. These two algorithms are effective means for equipment monitoring professionals to realize intelligent supervision of substations and equipment in the era of big data.
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