Identification and functional analysis of a chromosome 2D fragment harboring TaFPF1 gene with the potential for yield improvement using a late heading wheat mutant.

KEY MESSAGE: A chromosome fragment influencing wheat heading and grain size was identified using mapping of m406 mutant. The study of TaFPF1 in this fragment provides more insights into wheat yield improvement. In recent years, wheat production has faced formidable challenges driven by rapid population growth and climate change, emphasizing the importance of improving specific agronomic traits such as heading date, spike length, and grain size. To identify potential genes for improving these traits, we screened a wheat EMS mutant library and identified a mutant, designated m406, which exhibited a significantly delayed heading date compared to the wild-type. Intriguingly, the mutant also displayed significantly longer spike and larger grain size. Genetic analysis revealed that a single recessive gene was responsible for the delayed heading. Surprisingly, a large 46.58 Mb deletion at the terminal region of chromosome arm 2DS in the mutant was identified through fine mapping and fluorescence in situ hybridization. Thus, the phenotypes of the mutant m406 are controlled by a group of linked genes. This deletion encompassed 917 annotated high-confidence genes, including the previously studied wheat genes Ppd1 and TaDA1, which could affect heading date and grain size. Multiple genes in this region probably contribute to the phenotypes of m406. We further investigated the function of TaFPF1 using gene editing. TaFPF1 knockout mutants showed delayed heading and increased grain size. Moreover, we identified the direct upstream gene of TaFPF1 and investigated its relationship with other important flowering genes. Our study not only identified more genes affecting heading and grain development within this deleted region but also highlighted the potential of combining these genes for improvement of wheat traits.

TaMYB72 directly activates the expression of TaFT to promote heading and enhance grain yield traits in wheat (Triticum aestivum L.).

Heading date, grain number per spike, and grain weight are crucial traits affecting yield and adaptability in wheat. The transcription factor TaMYB72 is an important regulator of wheat grain yield and its knock-out mutants can be used as germplasm resources for wheat improvement.

Association between self-efficacy, spiritual well-being and the willingness to provide spiritual care among nursing staff in Taiwan: a cross-sectional study.

BACKGROUND: Spiritual care plays a significant role in holistic patient care, addressing not only physical ailments but also attending to patients' emotional and spiritual well-being. While the importance of spiritual care in nursing is widely recognized, there is often a gap in understanding nurses' willingness to provide such care. This cross-sectional study aimed to explore the association between self-efficacy, spiritual well-being, and willingness to provide spiritual care among nursing staff. METHODS: The study conducted a cross-sectional survey of full-time registered nurses at a hospital in Taiwan from January 2019 to December 2019. A sample comprising 168 nurses was selected for participation in the study through a random sampling method. In addition to collecting demographic variables, the assessment tools used in the study include the General Self-Efficacy Scale (GSES) for measuring self-efficacy, the Spiritual Index of Well-Being Chinese Version (SIWB-C) for evaluating spiritual well-being, and the Spiritual Care Needs Inventory (SCNI) to gauge willingness to provide spiritual care. RESULTS: Most participants in the study were female, accounting for 98.2% (n = 165). The mean age of all 168 nurses was 37.1 ± 9.3 years. Additionally, most participants held a Bachelor's degree (79.2%, n = 133) and possessed clinical experience was 10.5 ± 9.3 years. Through logistic regression analysis, it was found that regardless of whether participants have received sufficient spiritual care training, both GSES and SIWB-C remain influential factors in determining the provision of spiritual care. CONCLUSIONS: Collaboration between healthcare management and nursing staff is essential for fostering a healthcare environment that not only appreciates the physical and spiritual dimensions of patient care but also prioritizes the enhancement of nurses ' self-efficacy and well-being.

Practical Synthesis of Terminal Vinyl Fluorides.

The synthesis of di- and trisubstituted vinyl fluorides with high isomeric purity remains a challenge for organic synthesis. While many methods exist to access these compounds, the separation of the desired isomer from the minor isomer and/or starting materials often is difficult. Herein, we report a practical method to access di- and trisubstituted vinyl fluorides via a selective Horner-Wadsworth-Emmons olefination/hydrolysis, which provides crystalline 2-fluoroacrylic acids in high (>98%) E-isomeric purity. A subsequent silver-catalyzed stereoretentive decarboxylation provides the title substances with high isomeric purity and without the need for tedious chromatography to remove the minor isomer. The process was amenable to a variety of aldehydes and ketones and provided a diverse array of di- and trisubstituted vinyl fluorides. The sequence was applied to the synthesis of antibacterial and anti-inflammatory compounds.

Effects of oral stimulation with breast milk in preterm infants oral feeding: a randomized clinical trial.

OBJECTIVES: This study was performed to evaluate the effect of oral stimulation with breast milk for preterm infants. METHODS: A total of 68 subjects form neonatal intensive care unit were randomly assigned into control group (n=20), premature infant oral motor intervention (PIOMI) group (n=25) and premature infant oral motor intervention with breast milk (BM-PIOMI) group (n=23). RESULTS: BM-PIOMI group had significant shorter initiation of oral feeding (IOF) time compared to PIOMI group (2.95 days, 95% CI [0.42-5.48]) or control group (9.79 days, 95% CI [7.07-12.51]). BM-PIOMI group had significant sooner transition time from IOF to full oral feeding (FOF) compared to control group (6.68 days, 95% CI [2.2-11.16]), but not to PIOMI group (2.09 days, 95% CI [-2.07 to 6.25]). Length of hospital stay (LOS) did not show statistical different between three groups (control 38.85 ± 14.40 vs. PIOMI 38.48 ± 11.76 vs. BM-PIOMI 38.04 ± 12.2). Growth mixture model identified improvement in non-nutritive sucking (NNS) score in BM-PIOMI group compared to control and PIOMI group (0.8293, p<0.0001, and 0.8296, p<0.0001, respectively). CONCLUSIONS: Oral stimulation with breast milk can better promotes the oral feeding process of premature infants than the simple oral stimulation, by shorten IOF time and improve early NNS score, but does not shorten transition time from IOF to FOF and LOS.

Transcriptome profiling of developing leaf and shoot apices to reveal the molecular mechanism and co-expression genes responsible for the wheat heading date.

BACKGROUND: Wheat is one of the most widely planted crops worldwide. The heading date is important for wheat environmental adaptability, as it not only controls flowering time but also determines the yield component in terms of grain number per spike. RESULTS: In this research, homozygous genotypes with early and late heading dates derived from backcrossed progeny were selected to conduct RNA-Seq analysis at the double ridge stage (W2.0) and androgynous primordium differentiation stage (W3.5) of the leaf and apical meristem, respectively. In total, 18,352 differentially expressed genes (DEGs) were identified, many of which are strongly associated with wheat heading date genes. Gene Ontology (GO) enrichment analysis revealed that carbohydrate metabolism, trehalose metabolic process, photosynthesis, and light reaction are closely related to the flowering time regulation pathway. Based on MapMan metabolic analysis, the DEGs are mainly involved in the light reaction, hormone signaling, lipid metabolism, secondary metabolism, and nucleotide synthesis. In addition, 1,225 DEGs were annotated to 45 transcription factor gene families, including LFY, SBP, and MADS-box transcription factors closely related to flowering time. Weighted gene co-expression network analysis (WGCNA) showed that 16, 336, 446, and 124 DEGs have biological connections with Vrn1-5 A, Vrn3-7B, Ppd-1D, and WSOC1, respectively. Furthermore, TraesCS2D02G181400 encodes a MADS-MIKC transcription factor and is co-expressed with Vrn1-5 A, which indicates that this gene may be related to flowering time. CONCLUSIONS: RNA-Seq analysis provided transcriptome data for the wheat heading date at key flower development stages of double ridge (W2.0) and androgynous primordium differentiation (W3.5). Based on the DEGs identified, co-expression networks of key flowering time genes in Vrn1-5 A, Vrn3-7B, WSOC1, and Ppd-1D were established. Moreover, we discovered a potential candidate flowering time gene, TraesCS2D02G181400. Taken together, these results serve as a foundation for further study on the regulatory mechanism of the wheat heading date.

Establishing quality evaluation system of nursing management in fever clinics: A Delphi method.

AIM: The aim of this study is to construct a quality evaluation system for fever clinic nursing management. BACKGROUND: Fever clinic is the first line of defence against the epidemic during COVID-19 in China. METHODS: Our study combines the Delphi method and the analytic hierarchy process. Delphi method was used to carry out two rounds of consultation for 18 experts, to select and revise indicators at all levels. Analytic hierarchy process was used to calculate the weight of indicators at all levels. RESULTS: A quality evaluation system of nursing management for fever clinics is built using Delphi method. It includes five first-level indexes, 14 second-level indexes and 82 third-level indexes. A two-round expert consultation is used to build the indicators. The recovery rates of expert questionnaires in the two rounds were, respectively, 100% and 94%, and expert authority coefficients were 0.925. The Kendall coefficients in the two rounds were, respectively, 0.205 and 0.162 (P < .001). The weight analysis shows that health management of nursing staff (0.2803) and disinfection isolation and treatment of medical waste (0.2803) are most important, followed by nursing post management and personnel training (0.1889), configuration and management of equipment (0.1427) and patient consultation management and nursing (0.1078). CONCLUSION: The quality evaluation system of nursing management in the constructed fever clinic is used to put forward a specific, objective and quantifiable evaluation criteria of nursing quality for fever clinic management, which can better meet the needs of epidemic prevention and control, and has a certain application and promotion value. IMPLICATIONS FOR NURSING MANAGEMENT: The establishment and improvement of a quality system for fever clinic care management will help to respond to outbreaks such as COVID-19.

Effectiveness of palliative care consultation service on caregiver burden over time between terminally ill cancer and non-cancer family caregivers.

PURPOSE: The responsibility of taking care of terminal patients is accepted as a role of family members in Taiwan. Only a few studies have focused on the effect of palliative care consultation service (PCCS) on caregiver burden between terminal cancer family caregivers (CFCs) and non-cancer family caregivers (NCFCs). Therefore, the purpose of this study is to address the effect of PCCS on caregiver burden between CFC and NCFC over time. METHODS: A prospective longitudinal study was conducted in a medical center in northern Taiwan from July to November 2017. The participants were both terminally ill cancer and non-cancer patients who were prepared to receive PCCS, as well as their family caregivers. Characteristics including family caregivers and terminal patients and Family Caregiver Burden Scale (FCBS) were recorded pre-, 7, and 14 days following PCCS. A generalized estimating equation model was used to analyze the change in the level of family caregiver burden (FCB) between CFC and NCFC. RESULTS: The study revealed that there were no statistically significant differences in FCB between CFC and NCFC 7 days and 14 days after PCCS (p > 0.05). However, FCB significantly decreased in both CFC and NCFC from pre-PCCS to 14 days after PCCS (ß = - 12.67, p = 0.013). PPI of patients was the key predictor of FCB over time following PCCS (ß = 1.14, p = 0.013). CONCLUSIONS: This study showed that PCCS can improve FCB in not only CFC but also NCFC. We suggest that PCCS should be used more widely in supporting family caregivers of terminally ill patients to reduce caregiver burden.

Autophagy inhibits TLR4-mediated invasiveness of oral cancer cells via the NF-κB pathway.

OBJECTIVES: Toll-like receptor 4 (TLR4) is abnormally expressed in oral cancer tissues and promotes cancer cell invasion. The purpose of this study was to clarify the mechanism by which autophagy regulates oral cancer invasion through the TLR4-NF-κB pathway. SUBJECTS AND METHODS: We examined TLR4 expression in oral cancer tissues and analysed the relationship between its expression and clinicopathological features. The invasion and migration of LPS-stimulated oral cancer cells with up- or downregulation of TLR4 expression was detected in addition to NF-κB signalling and autophagy levels. Furthermore, the role of autophagy in regulating TLR4-mediated cell invasiveness was explored by silencing the expression of key autophagy genes ATG7 and p62. RESULTS: We found that TLR4 overexpression was closely related to cervical lymphatic metastasis and poor survival. TLR4 activated the NF-κB pathway to promote the invasiveness of OSCC cells, and autophagy partly inhibited invasiveness by suppressing the NF-κB pathway. We observed that p62 translocated from the cytoplasm to the nucleus when autophagy was activated by LPS. Finally, silencing p62 further promoted LPS-mediated cell invasiveness. CONCLUSION: Toll-like receptor 4 significantly enhanced the invasiveness of OSCC cells. Autophagy may regulate cell invasiveness through the NF-κB pathway by modulating both the cytoplasmic and nuclear levels of p62.

Precisely Tuning Photothermal and Photodynamic Effects of Polymeric Nanoparticles by Controlled Copolymerization.

Cancer possesses normoxic and hypoxia microenvironments with different levels of oxygen, needing different efficacies of photothermal and photodynamic therapies. It is important to precisely tune the photothermal and photodynamic effects of phototherapy nano-agents for efficient cancer treatment. Now, a series of copolymeric nanoparticles (PPy-Te NPs) were synthesized in situ by controlled oxidative copolymerization with different ratios of pyrrole to tellurophene by FeCl3 . The photothermal and photodynamic effects of semiconducting nano-agents under the first near-infrared (NIR) irradiation were precisely and systematically tuned upon simply varying the molar ratio of the pyrrole to tellurophene. The PPy-Te NPs were used for cancer treatment in mice, exhibiting excellent biocompatibility and therapeutic effect. This work presents a simple method to tune photothermal and photodynamic therapies effect in semiconducting nano-agents for cancer treatment.

Discovery and optimization of oxadiazole-based FLAP inhibitors.

Structure activity relationship (SAR) investigation of an oxadiazole based series led to the discovery of several potent FLAP inhibitors. Lead optimization focused on achieving functional activity while improving physiochemical properties and reducing hERG inhibition. Several compounds with favorable in vitro and in vivo properties were identified that were suitable for advanced profiling.

Psychometric properties of the Chinese version of Spiritual Index of Well-Being in elderly Taiwanese.

BACKGROUND: Spiritual well-being has become an increasingly important issue for the elderly people. The 12-item Spirituality Index of Well-Being (SIWB) is a well-validated instrument for assessing a patient's current spiritual state. However, the psychometric properties of the SIWB in the Chinese elderly populations are not known. Therefore, this study translated the SIWB into Chinese and evaluated its psychometric properties. METHODS: The English version of the SIWB was first translated into Chinese based on the Brislin's translation model. The psychometric properties of the translated version of the SIWB (SIWB-C) was evaluated in 416 elderly Taiwanese recruited using a purposive sampling procedure from a medical center, a long-term care institution, and a community health center. Convergent validity was accessed using Pearson's correlation coefficients of the SIWB-C, the EQ-5D-3 L health-related quality of life scale, and the Geriatric Depression Scale-5 (GDS-5). Exploratory factor analysis with Varimax rotation was performed to determine the construct validity. Confirmatory factor analysis was conducted for verification of the quality of the factor structures and demonstrating the convergent validity of the SIWB-C. An internal consistency test based on the Cronbach's alpha coefficient and a stability test based on the Guttman split-half coefficient were also performed. Test-retest reliability was evaluated with intraclass correlation coefficient. RESULTS: Exploratory factor analysis confirmed the original two-dimensional structure of the scale. Confirmatory factor analysis indicated a well-fitting model and a fine convergent validity of the SIWB-C. The Cronbach's alpha coefficient and the Guttman split-half coefficient for the SIWB-C were 0.94 and 0.84, respectively. The correlations between the SIWB-C with EQ-5D-3 L and GDS-5 were 0.22 (p < 0.01) and 0.45 (p < 0.05), respectively. The intraclass correlation coefficient of the SIWB-C over a test-retest interval of two weeks was 0.989. CONCLUSIONS: The SIWB-C was found to be a potential useful measure of subjective spiritual well-being in elderly Taiwanese. Its application in assessing the spiritual well-being in Mandarin-speaking elderly population warrants further investigation.

Path modeling of knowledge, attitude and practice toward palliative care consultation service among Taiwanese nursing staff: a cross-sectional study.

BACKGROUND: The Taiwanese government has promoted palliative care consultation services (PCCS) to support terminally ill patients in acute ward settings to receive palliative care since 2005. Such an intervention can enhance the quality of life and dignity of terminally ill patients. However, research focusing on the relationship between the knowledge, attitude and practice of a PCCS using path modelling in nursing staff is limited. Therefore, the aim of this study was to elucidate the effect of path modeling on the knowledge, attitude and practice toward PCCS in Taiwanese nursing staff. METHODS: This was a cross-sectional, descriptive study design using convenience sampling. Data collected included demographics, knowledge, attitude and practice as measured by the PCCS inventory (KAP-PCCSI). Two hundred and eighty-four nursing staff from a medical center in northern Taiwan participated in the study in 2013. We performed descriptive statistics, regression analysis, and path modeling using SPSS 19.0 and set p < 0.05 as the statistical significance threshold. RESULTS: The results showed that the identical factor significantly associated with knowledge, attitude, and practice toward PCCS among nurses was the frequency of contact with PCCS. In addition, higher level of knowledge toward PCCS was associated with working in haematology and oncology wards, and participation in education related to palliative care. A more positive attitude toward PCCS was associated with working in a haematology and oncology ward, and experience of friends or relatives dying. Higher level of practice toward PCCS was associated with nurses who participated in education related to palliative care. In the path modeling, we found that holders of a master's degree indirectly positive affected practice toward PCCS. Possession of a bachelor degree or above, being single, working within a haematology and oncology ward, and frequency of contact with PCCS positively affected practice toward PCCS. CONCLUSIONS: Based on this study, it is proposed that consultation with PCCS has a positive impact on the care of terminally ill patients. Encouragement of staff to undertake further education can improve the practice of ward staff providing palliative care.

Randomized controlled trial of a six-week spiritual reminiscence intervention on hope, life satisfaction, and spiritual well-being in elderly with mild and moderate dementia.

OBJECTIVE: Reminiscence therapy has been reported to improve the well-being in patients with dementia. However, few studies have examined the effects of spiritual reminiscence, which emphasizes on reconnecting and enhancing the meaning of one's own experience, on patients with dementia. Therefore, this study aimed to investigate the effects of spiritual reminiscence on hope, life satisfaction, and spiritual well-being in elderly Taiwanese with mild or moderate dementia. METHODS: A randomized controlled trial was conducted on 103 patients with mild or moderate dementia recruited from a medical center in central Taiwan. The patients were randomly assigned to either a 6-week spiritual reminiscence group (n = 53) or control group (n = 50). The Herth Hope Index, the Life Satisfaction Scale, the Spirituality Index of Well-Being were administered before and after the 6-week period. RESULTS: The interaction terms between group and time for the three outcome measures were found to be significant (P < 0.001), indicating that the changes over time in them were different between the intervention and control groups. CONCLUSIONS: Findings of this randomized controlled trial showed that hope, life satisfaction, and spiritual well-being of elderly patients with mild or moderate dementia could significantly be improved with a 6-week spiritual reminiscence intervention.

Relationship between palliative care consultation service and end-of-life outcomes.

PURPOSE: Palliative care consultation service (PCCS) is currently utilized to provide care to terminal patients in Taiwan. However, there is little research on the relationship between PCCS and end-of-life outcomes. This study aimed to elucidate the association between PCCS and end-of-life outcomes in terminal cancer patients. METHODS: Retrospective chart reviews of terminal cancer patients who consulted the PCCS of a medical center in Taiwan from January 2007 to December 2012 were performed. Data on 1369 patients were recorded, which included details of outcomes such as discharge from hospital, transfer to hospice ward, and death after PCCS termination. Other variables such as demographics, disease-related information, symptoms, and psychosocial needs were also evaluated. Logistic regression models were employed to estimate the adjusted odds ratios and related 95% confidence intervals. RESULTS: The Eastern Cooperative Oncology Group performance status, timing of do-not-resuscitate (DNR) signature, constipation, and spiritual problems experienced by the patients were important predictors for terminal cancer patients who were discharged from the hospital or had expired at the time of PCCS termination. Age, gender, primary cancer diagnosis, timing of DNR signature, constipation, and other physical symptoms were the key predictors for patients who were transferred to the hospice ward or had expired. CONCLUSIONS: This study confirms the outcomes of PCCS and highlights the important predictors for patients at PCCS termination. These factors can be targeted to improve and enhance the quality of PCCS rendered in the future.

Selective CB2 receptor agonists. Part 1: the identification of novel ligands through computer-aided drug design (CADD) approaches.

Computer-aided drug design scaffold hopping strategies were utilized to identify new classes of CB2 agonists when compounds of an established series with low nanomolar potency were challenging to optimize for good drug-like properties. Use of ligand-based design strategies through BI Builder (a tool for de novo design) and PharmShape (a virtual screening software package) approaches led to the discovery of new chemotypes. Specifically, compounds containing azetidine-, proline-, and piperidine-based cores were found to have low nanomolar and picomolar CB2 agonist activities with drug-like properties considered appropriate for early profiling.

Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds.

Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.

Selective CB2 receptor agonists. Part 3: the optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model.

A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.

Blumea balsamifera Oil for the Acceleration of Healing of Burn Injuries.

Blumea balsamifera oil (BBO) is a main extract obtained from Blumea balsamifera (L.) DC (Ainaxiang) leaves, which are widely used as a traditional medicine by the Miao and Li Nations to promote skin trauma or burn injury healing. This study was initiated to investigate the healing efficacy in deep second-degree burn model in rats. The rats were treated by BBO for 21 consecutive days. The rate of healing, scabs dropped time and re-epithelialization time were observed every three days for 21 days after burn injury. The samples were collected from different treated rats by sacrificing the animals on the 1st, 2nd, 5th, 9th, 14th, and 21st day post-burn creation. Then, the water content of burn tissue was measured. Plasma interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) levels were evaluated, and the tissue expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-ß) were determined along with skin histopathology. The results showed that the water content of tissue was significantly reduced, the scabs dropped time shortened, and healing accelerated after treatment with BBO in the burn injury rats. Furthermore, the expressions of growth factors were significantly increased in the tissue; however, the levels of inflammatory factors on plasma decreased. This study confirms the efficacy of BBO consumption on burn injuries.

Concordance between nurses' perception of their ability to provide spiritual care and the identified spiritual needs of hospitalized patients: A cross-sectional observational study.

Spiritual care is essential to the well-being of patients, and nurses provide spiritual care as a fundamental part of nursing practice. In this study, we investigated the spiritual care needs of hospitalized patients to determine whether the perceived knowledge of nurses corresponded with these spiritual care needs. A cross-sectional study was conducted on 1351 hospitalized patients and 200 registered nurses recruited from a medical center in central Taiwan. A questionnaire, including the 21-item Spiritual Care Needs Inventory (patient and nurse version) and basic demographic information, was distributed to eligible participants. The top three items of the spiritual care needs expressed by the hospitalized patients were respect for privacy and dignity, showing concern, and guidance in gaining a sense of hope in life; the percentages of nurses not knowing how to provide these spiritual care needs were 0%, 1%, and 15%, respectively. The spiritual care needs of patients showed a significant relationship with the knowledge of nurses, suggesting that the perceived knowledge of the nurses generally corresponded with the spiritual care items that the patients required most.