Dietary limonene promotes gastrointestinal barrier function via upregulating tight/adherens junction proteins through cannabinoid receptor type-1 antagonistic mechanism and alters cellular metabolism in intestinal epithelial cells.

Limonene, a dietary monocyclic monoterpene commonly found in citrus fruits and various aromatic plants, has garnered increasing interest as a gastrointestinal protectant. This study aimed to assess the effects of limonene on intestinal epithelial barrier function and investigate the involvement of cannabinoid receptor type-1 (CB1R) in vitro. Additionally, the study focused on examining the metabolomic changes induced by limonene in the intestinal epithelial cells (Caco-2). Initial analysis of transepithelial electrical resistance (TEER) revealed that both l-limonene and d-limonene, isomers of limonene, led to a dose- and time-dependent increase in TEER in normal cells and those inflamed by pro-inflammatory cytokines mixture (CytoMix). Furthermore, both types of limonene reduced CytoMix-induced paracellular permeability, as demonstrated by a decrease in Lucifer yellow flux. Moreover, d-limonene and l-limonene treatment increased the expression of tight junction molecules (TJs) such as occludin, claudin-1, and ZO-1, at both the transcriptional and translational levels. d-Limonene upregulates E-cadherin, a molecule involved in adherens junctions (AJs). Mechanistic investigations demonstrated that d-limonene and l-limonene treatment significantly inhibited CB1R at the protein, while the mRNA level remained unchanged. Notably, the inhibitory effect of d-limonene on CB1R was remarkably similar to that of pharmacological CB1R antagonists, such as rimonabant and ORG27569. d-limonene also alters Caco-2 cell metabolites. A substantial reduction in ß-glucose and 2-succinamate was detected, suggesting limonene may impact intestinal epithelial cells' glucose uptake and glutamate metabolism. These findings suggest that d-limonene's CB1R antagonistic property could effectively aid in the recovery of intestinal barrier damage, marking it a promising gastrointestinal protectant.

Computationally designed mRNA-launched protein nanoparticle vaccines.

Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.

Using a static magnetic field to attenuate the severity in COVID-19-invaded lungs.

Two important factors affecting the progress of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the S-protein binding function of ACE2 receptors and the membrane fluidity of host cells. This study aimed to evaluate the effect of static magnetic field (SMF) on S-protein/ACE2 binding and cellular membrane fluidity of lung cells, and was performed in vitro using a Calu-3 cell model and in vivo using an animal model. The ability of ACE2 receptors to bind to SARS-CoV-2 spike protein on host cell surfaces under SMF stimulation was evaluated using fluorescence images. Host lung cell membrane fluidity was tested using fluorescence polarization to determine the effects of SMF. Our results indicate that 0.4 T SMF can affect binding between S-protein and ACE2 receptors and increase Calu-3 cell membrane fluidity, and that SMF exposure attenuates LPS-induced alveolar wall thickening in mice. These results may be of value for developing future non-contact, non-invasive, and low side-effect treatments to reduce disease severity in COVID-19-invaded lungs.

Progesterone modulates cell growth via integrin αvß3-dependent pathway in progesterone receptor-negative MDA-MB-231 cells.

Progesterone (P4) plays a pivotal role in regulating the cancer progression of various types, including breast cancer, primarily through its interaction with the P4 receptor (PR). In PR-negative breast cancer cells, P4 appears to function in mediating cancer progression, such as cell growth. However, the mechanisms underlying the roles of P4 in PR-negative breast cancer cells remain incompletely understood. This study aimed to investigate the effects of P4 on cell proliferation, gene expression, and signal transduction in PR-negative MDA-MB-231 breast cancer cells. P4-activated genes, associated with proliferation in breast cancer cells, exhibit a stimulating effect on cell growth in PR-negative MDA-MB-231 cells, while demonstrating an inhibitory impact in PR-positive MCF-7 cells. The use of arginine-glycine-aspartate (RGD) peptide successfully blocked P4-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation, aligning with computational models of P4 binding to integrin αvß3. Disrupting integrin αvß3 binding with RGD peptide or anti-integrin αvß3 antibody altered P4-induced expression of proliferative genes and modified P4-induced cell growth in breast cancer cells. In conclusion, integrin αvß3 appears to mediate P4-induced ERK1/2 signal pathway to regulate proliferation via alteration of proliferation-related gene expression in PR-negative breast cancer cells.

Viscolin-mediated antiapoptotic and neuroprotective effects in cortical neurons exposed to oxygen-glucose deprivation and rats subjected to transient focal cerebral ischemia.

OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.

Rumen and hindgut microbiome regulate average daily gain of preweaning Holstein heifer calves in different ways.

BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.

Automatic planning for functional lung avoidance radiotherapy based on function-guided beam angle selection and plan optimization.

Objective.This study aims to develop a fully automatic planning framework for functional lung avoidance radiotherapy (AP-FLART).Approach.The AP-FLART integrates a dosimetric score-based beam angle selection method and a meta-optimization-based plan optimization method, both of which incorporate lung function information to guide dose redirection from high functional lung (HFL) to low functional lung (LFL). It is applicable to both contour-based FLART (cFLART) and voxel-based FLART (vFLART) optimization options. A cohort of 18 lung cancer patient cases underwent planning-CT and SPECT perfusion scans were collected. AP-FLART was applied to generate conventional RT (ConvRT), cFLART, and vFLART plans for all cases. We compared automatic against manual ConvRT plans as well as automatic ConvRT against FLART plans, to evaluate the effectiveness of AP-FLART. Ablation studies were performed to evaluate the contribution of function-guided beam angle selection and plan optimization to dose redirection.Main results.Automatic ConvRT plans generated by AP-FLART exhibited similar quality compared to manual counterparts. Furthermore, compared to automatic ConvRT plans, HFL mean dose,V20, andV5were significantly reduced by 1.13 Gy (p< .001), 2.01% (p< .001), and 6.66% (p< .001) respectively for cFLART plans. Besides, vFLART plans showed a decrease in lung functionally weighted mean dose by 0.64 Gy (p< .01),fV20by 0.90% (p= 0.099), andfV5by 5.07% (p< .01) respectively. Though inferior conformity was observed, all dose constraints were well satisfied. The ablation study results indicated that both function-guided beam angle selection and plan optimization significantly contributed to dose redirection.Significance.AP-FLART can effectively redirect doses from HFL to LFL without severely degrading conventional dose metrics, producing high-quality FLART plans. It has the potential to advance the research and clinical application of FLART by providing labor-free, consistent, and high-quality plans.

Translation, Cultural Adaptation and Validation of the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) in Chinese.

BACKGROUND: Rhinoplasty requires balanced consideration of function and aesthetics, necessitating a precise evaluation tool. A reliable and validated patient-reported measure, the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) evaluates both aspects but was previously unavailable in Chinese. This study fills that gap by providing a Chinese version. OBJECTIVES: This study aims to translate, culturally adapt, and validate a Chinese iteration of the SCHNOS (C-SCHNOS) for appraising the functional and aesthetic outcomes among Chinese patients post-rhinoplasty, furnishing a reliable and efficacious assessment tool for Chinese users. METHODS: Following international guidelines, the SCHNOS questionnaire was translated and culturally adapted for Chinese use. Its psychometric properties, including internal consistency, correlations, and reproducibility, were evaluated among Chinese natives in Sichuan Province from March 2022 to January 2023. RESULTS: The C-SCHNOS was administered to 110 Chinese natives, showing high internal consistency, Cronbach's α of 0.81 for SCHNOS-O (Obstructive domain), 0.92 for SCHNOS-C (Cosmetic domain). Spearman correlations for SCHNOS-O (0.36-0.65) and SCHNOS-C (0.51-0.74) were positive and significant. Test-retest reliability analyses revealed strong Spearman correlations for SCHNOS-O (r=0.87) and SCHNOS-C (r=0.90). Responsiveness was statistically significant for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P=0.222). Exploratory factor analysis and parallel tests indicated that C-SCHNOS maintained a single-factor structure, with eigenvalues exceeding the critical values (2.55 for SCHNOS-O and 4.35 for SCHNOS-C), reflecting excellent unidimensionality. CONCLUSIONS: The SCHNOS questionnaire was successfully translated into Chinese and culturally adapted. The C-SCHNOS is a dependable and valid instrument for use in Chinese population undergoing functional or cosmetic rhinoplasty.

Glutathione determines chronic myeloid leukemia vulnerability to an inhibitor of CMPK and TMPK.

Bcr-Abl transformation leads to chronic myeloid leukemia (CML). The acquirement of T315I mutation causes tyrosine kinase inhibitors (TKI) resistance. This study develops a compound, JMF4073, inhibiting thymidylate (TMP) and cytidylate (CMP) kinases, aiming for a new therapy against TKI-resistant CML. In vitro and in vivo treatment of JMF4073 eliminates WT-Bcr-Abl-32D CML cells. However, T315I-Bcr-Abl-32D cells are less vulnerable to JMF4073. Evidence is presented that ATF4-mediated upregulation of GSH causes T315I-Bcr-Abl-32D cells to be less sensitive to JMF4073. Reducing GSH biosynthesis generates replication stress in T315I-Bcr-Abl-32D cells that require dTTP/dCTP synthesis for survival, thus enabling JMF4073 susceptibility. It further shows that the levels of ATF4 and GSH in several human CML blast-crisis cell lines are inversely correlated with JMF4073 sensitivity, and the combinatory treatment of JMF4073 with GSH reducing agent leads to synthetic lethality in these CML blast-crisis lines. Altogether, the investigation indicates an alternative option in CML therapy.

Bioinspired Nanolayered Structure Tuned by Extensional Stress: A Scalable Way to High-Performance Biodegradable Polyesters.

The nacre-inspired multi-nanolayer structure offers a unique combination of advanced mechanical properties, such as strength and crack tolerance, making them highly versatile for various applications. Nevertheless, a significant challenge lies in the current fabrication methods, which is difficult to create a scalable manufacturing process with precise control of hierarchical structure. In this work, a novel strategy is presented to regulate nacre-like multi-nanolayer films with the balance mechanical properties of stiffness and toughness. By utilizing a co-continuous phase structure and an extensional stress field, the hierarchical nanolayers is successfully constructed with tunable sizes using a scalable processing technique. This strategic modification allows the robust phase to function as nacre-like platelets, while the soft phase acts as a ductile connection layer, resulting in exceptional comprehensive properties. The nanolayer-structured films demonstrate excellent isotropic properties, including a tensile strength of 113.5 MPa in the machine direction and 106.3 MPa in a transverse direction. More interestingly, these films unprecedentedly exhibit a remarkable puncture resistance at the same time, up to 324.8 N mm-1, surpassing the performance of other biodegradable films. The scalable fabrication strategy holds significant promise in designing advanced bioinspired materials for diverse applications.

Effects of Sapindus mukorossi Seed Oil on Bone Healing Efficiency: An Animal Study.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

Composition Characterization of Cinnamomum osmophloeum Kanehira Hydrosol and Its Enhanced Effects on Erectile Function.

Cinnamomum osmophloeum Kanehira (CO) is an endemic species of Taiwan. This study elucidated the composition of CO hydrosol, revealing trans-cinnamaldehyde (65.03%), trans-cinnamyl acetate (7.57%), and coumarin (4.31%) as the main volatile compounds. Seven compounds were identified in the water fraction of hydrosol, including a novel compound, 2-(2-hydroxyphenyl)oxetan-3-ol. This marks the first investigation into high-polarity compounds in hydrosol, extending beyond the volatile components. Notably, two compounds, trans-phenyloxetan-3-ol and cis-phenyloxetan-3-ol, demonstrated significant inhibition activity against phosphodiesterase type five (PDE5), with IC50 values of 4.37 µM and 3.40 µM, respectively, indicating their potential as novel PDE5 inhibitors. Furthermore, CO hydrosol was evaluated against enzymes associated with erectile dysfunction, namely acetylcholinesterase (AChE), angiotensin-I converting enzyme (ACE), and arginase type 2 (ARG2). These findings underscore the potential of CO hydrosol to modulate erectile function through diverse physiological pathways, hinting at its prospects for future development in a beverage or additive with enhanced effects on erectile function.

Anti-oxidative and anti-inflammatory effects of Ginkgo biloba extract (EGb761) on hindlimb skeletal muscle ischemia-reperfusion injury in rats.

In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.

Angle-based minimally invasive glaucoma surgery in normal tension glaucoma: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis quantitatively examines the efficacy of angle-based minimally invasive glaucoma surgery (MIGS) in normal tension glaucoma (NTG). METHODS: A literature search was performed on Medline, Embase, PubMed, CINAHL and Cochrane Library from inception until 20 December 2022. Pilot, cohort, observational studies and randomised controlled trials including at least 5 subjects undergoing angle-based MIGS (trabecular-bypass devices, excisional trabeculotomy, goniotomy and ab-interno canaloplasty) for NTG, with or without cataract surgery, were included. Meta-analysis of continuous outcome using the meta routine in R version 2022.12.0+353 was performed to determine mean intraocular pressure (IOP) and anti-glaucoma medication (AGM) reduction post-operatively. RESULTS: Of the 846 studies initially identified, 15 studies with a pooled total of 367 eyes which underwent combined phacoemulsification and angle-based MIGS were included for final meta-analysis. Outcomes of the iStent were reported in 5 studies, iStent inject in 7 studies, Hydrus Microstent in 1 study, Kahook Dual Blade in 3 studies, and Trabectome in 2 studies. There was significant reduction in both IOP and AGM post-operatively at 6 months (2.44 mmHg, 95%CI: 1.83-3.06; 1.21 AGM, 95%CI: 0.99-1.44), 12 months (2.28 mmHg, 95%CI: 1.71-2.84; 1.18 AGM, 95%CI: 0.90-1.47), 24 months (2.10 mmHg, 95%CI: 1.51-2.68; 1.26 AGM, 95%CI: 0.85-1.68) and 36 months (2.43 mmHg, 95%CI: 1.71-3.15, 0.87 AGM, 95%CI: 0.21-1.53) (all p < 0.05). Subgroup analysis on combined phacoemulsification-iStent inject surgery demonstrated a reduction in both IOP (2.31 mmHg, 95%CI: 1.07-3.56, p < 0.001) and AGM (1.07 AGM, 95%CI: 0.86-1.29, p < 0.001) at 12 months post-operatively. CONCLUSIONS: Angle-based MIGS combined with phacoemulsification effectively reduces IOP and AGM in NTG eyes for up to 36 months after surgery.

Pediatric Emergent Peritoneal Dialysis in Intensive Care Units: Indications, Techniques, and Outcomes.

INTRODUCTION: This study aimed to identify risk factors affecting outcomes in pediatric patients requiring emergent peritoneal dialysis (PD) for all causes, focusing on survival rates, kidney function recovery, PD duration, complications, and quality of life. METHODS: A retrospective review was conducted on medical records of pediatric patients who received emergent bedside PD in the intensive care unit from January 2010 to February 2023. Thirty-four catheters were placed, with demographic, preoperative, and procedural data collected. MedCalc® Statistical Software was used for analysis with a significance level set at p < 0.05. Prophylactic antibiotics were administered prior to surgery, and catheters were placed using a consistent technique by a single team of pediatric surgeons. RESULTS: The median age at catheter placement was 39 days (range 2-2,286), and the median body weight was 3.53 kg (range 1.2-48.8). The majority were male (64.7%), with 17.6% preterm. The most common indication for PD was acute kidney injury (AKI) (88.2%), followed by hyperammonemia, metabolic acidosis, and abdominal compartment syndrome. The median waiting period for PD placement was 1 day, and the median duration of PD was 7 days. Complications included dialysate leakage (22.8%) and catheter obstruction leading to PD discontinuation (31.4%). The mortality rate was high at 71.4%. CONCLUSION: It is advisable to advocate for the early initiation of PD in pediatric patients following cardiac surgery. AKI is a significant risk factor for mortality, while prematurity increases the risk of dialysate leakage. Omentectomy and the method of catheter exit did not significantly affect outcomes. The study's limitations highlight the need for larger prospective studies to better understand and improve emergent PD management in this vulnerable population.

Singlet oxygen production of Zn-Ag-In-S quantum dots for photodynamic treatment of cancer cells and bacteria.

Zn-Ag-In-S (ZAIS) quantum dots (QDs) were synthesized with various Ag-to-In ratios and used as novel photosensitizers for photodynamic therapy (PDT) on cancer cell inhibition and bacterial sterilization, and their structural, optical, and photodynamic properties were investigated. The alloyed QDs displayed a photoluminescence quantum yield of 72% with a long fluorescence lifetime of 5.3 µs when the Ag-to-In ratio was 1:3, suggesting a good opportunity as a dual functional platform for fluorescence imaging and PDT. The ZAIS QDs were then coated with amphiphilic brush copolymer poly(maleic anhydride-alt-1-octadecene) (PMAO) before application. The 1O2 quantum yield of the ZAIS/PMAO was measured to be 8%, which was higher than previously reported CdSe QDs and comparable to some organic photosensitizers. Moreover, the ZAIS QDs showed excellent stability in aqueous and biological media, unlike organic photosensitizers that tend to degrade over time. The in vitro PDT against human melanoma cell line (A2058) and Staphylococcus aureus shows about 30% inhibition rate upon 20 min light irradiation. Cell staining images clearly demonstrated that co-treatment with ZAIS QDs and light irradiation effectively killed A2058 cells, demonstrating the potential of ZAIS QDs as novel and versatile photosensitizers for PDT in cancer and bacterial treatment, and provides useful information for future designing of QD-based photosensitizers.

Abietane Diterpenoids from the Bark of Cryptomeria japonica and Their Antifungal Activities against Wood Decay Fungi.

Phytochemical investigation of the bark of Cryptomeria japonica led to the isolation of five new abietane diterpenoids, 5-epi-12-hydroxy-6-nor-5,6-secoabieta-8,11,13-trien-7,5-olide (1), 12-hydroxy-6ß-methoxy-6,7-secoabieta-8,11,13-trien-7,6-olide (2), 6ß,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (4), 5,12-dihydroxy-7,8-secoabieta-8,11,13-trien-7,8-olide (5), and 5α,8-epoxy-12-hydroxy-7,8-secoabieta-8,11,13-trien-7-al (6), together with one known abietane diterpenoid, obtuanhydride (3). Their structures were elucidated by analysis of spectroscopic data and comparison with the spectral data of known analogs. At the concentration of 100 µg/mL, compounds 4, 5, and 6 inhibited antifungal activities against wood decay fungi activity by 18.7, 37.2, and 46.7%, respectively.

Impact of COVID-19 on pediatric surgical practice in Taiwan: a comprehensive analysis.

Background: The COVID-19 pandemic has profoundly impacted global healthcare systems, causing significant disruptions in various medical practices. This study focuses on the specific effects of the pandemic on pediatric surgical practice in Taiwan, a region known for its effective public health measures and proximity to the initial outbreak. Methods: The study analyzes data from January 2020 to August 2022, comparing it with historical records from January 2017 to August 2019. It examines changes in surgical case volumes, patient demographics, surgical indications, and trends in preoperative evaluations, surgical procedures, and postoperative care. Results: The study reveals a decrease in total surgical cases from 2,255 to 1,931 during the pandemic. Notable findings include a slight increase in the average age of patients (4.81 to 5.10 years, p = 0.064), a significant shift in gender distribution towards male patients (68.9% to 73.5%, p = 0.0009), and changes in the types of surgical procedures performed, with head and neck and gastrointestinal surgeries seeing an increase. The average hospital stay lengthened, and certain specific surgical diseases, like hypospadias and liver tumors, showed an increase. However, the age distribution of pediatric surgical patients remained stable, and emergency surgical care was resiliently maintained. Discussion: The findings demonstrate the adaptability of Taiwan's healthcare system in maintaining pediatric surgical care during the pandemic. The study highlights a significant gender disparity in surgical interventions and a shift towards more urgent and emergent care, reflecting the reorganization of healthcare services during this period. The study's limitations include its retrospective nature and focus on a single institution. Conclusion: This research contributes valuable insights into the impact of the COVID-19 pandemic on pediatric surgical practice in Taiwan. It underscores the importance of adaptable healthcare strategies in ensuring continuity and quality of care during public health emergencies. Future research should focus on multi-institutional data and prospective studies to further understand these dynamics.

Response of carbon fixation, allocation, and growth to source-sink manipulation by defoliation in vegetative citrus trees.

Source-sink balance in plants determines carbon distribution, and altering it can impact carbon fixation, transport, and allocation. We aimed to investigate the effect of altered source-sink ratios on carbon fixation, transport, and distribution in 'Valencia' sweet orange (Citrus x sinensis) by various defoliation treatments (0%, 33%, 66%, and 83% leaf removal). Gas exchange parameters were measured on 0 and 10 days after defoliation using A/Ci response curves, and leaf export was measured two days after defoliation using radioisotope tracer techniques. Greater defoliation increased the maximum rate of carboxylation (Vcmax), electron transport rate (J1200), and triose-phosphate utilization rate (TPU). Leaf export was unaffected by defoliation but increased in leaves closer to the shoot apex. Basipetal translocation velocity in the trunk remained unaltered, indicating that more photosynthates remained in the shoot rather than being transported directly to the root sink. Defoliated plants initiated more new flush shoots but accumulated less shoot biomass per plant after 8 weeks. Carbon allocation to fine roots was smaller in defoliated plants, suggesting defoliation led to retention of carbohydrates in aboveground organs such as the trunk and other shoots from previous growing cycles. In conclusion, the low source-sink ratio increased carbon fixation without impacting individual leaf export in citrus. The results suggest that intermediate sinks such as the aboveground perennial organs play a role in mediating the translocation velocity. Further research is necessary to better understand the dynamics of source-sink regulation in citrus trees.

Development of a zinc chloride-based chemo-mechanical system for potential minimally invasive dental caries removal system.

Background/purpose: The chemo-mechanical caries-removal technique is known to offer advantages of selective dentin caries treatment while leaving healthy dental tissues intact. However, current sodium hypochlorite based reagents usually excessively damage dentin collagen. Therefore, the purpose of this study was to develop a novel chemo-mechanical caries-removal system to preserve the collagen network for subsequent prosthetic restorations. Materials and methods: The calfskin-derived collagen was chosen as a model system to investigate the dissolution behavior of collagen under different operating conditions of chemical-ultrasonic treatment systems. The molecular weight, triple-helix structure, the morphology, and functional group of collagen after treatment were investigated. Results: Various concentrations of sodium hypochlorite or zinc chloride together with ultrasonic machinery were chosen to investigate. The outcomes of circular dichroism (CD) spectra demonstrated stability of the triple-helix structure after treatment of a zinc chloride solution. In addition, two apparent bands at molecular weights (MWs) of 130 and 121 kDa evidenced the stability of collagen network. The positive 222 nm and 195 nm negative CD absorption band indicated the existence of a triple-helix structure for type I collagen. The preservation of the morphology and functional group of the collagen network on the etched dentin surface were investigated by in vitro dentin decalcification model. Conclusion: Unlike NaOCl, the 5 wt% zinc chloride solution combined with ultra-sonication showed dissolution rather than denature as well as degradation of the dentin collagen network. Additional in vivo evaluations are needed to verify its usefulness in clinical applications.