Search

In this work, we introduce the theoretical framework of the phonon-mediated Migdal effect for neutrino-nucleus scattering in semiconductors, considering both the Standard Model and the presence of the neutrino magnetic moment. We calculate the rate of electron excitation resulting from the Migdal effect and observe a substantial coherent enhancement compared to ordinary neutrino-electron scattering. Furthermore, we provide numerical sensitivities for detecting the Migdal effect and constraints on the neutrino magnetic moment, utilizing an experimental setup with reactor neutrinos.

Background: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. Objective: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. Methods: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. Results: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). Conclusion: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction

Summary: A better understanding of the molecular mechanism involving the lncRNA-miRNA-mRNA network underlying radiation damage can be beneficial for radioprotection. This study was designed to investigate the potential role of lncRNA NEAT1, miR-147 and Phosphoinositide Dependent Protein Kinase 1 (PDPK1) interaction in radioprotection by troxerutin (TRT). We first demonstrated that NEAT1 sponged miR-147, and PDPK1 mRNA was the primary target of miR-147. In the cells, the NEAT1 and PDPK1 levels were downregulated after the radiation but increased after the treatment with TRT. The miR-147 level was significantly induced by radiation and inhibited by TRT. NEAT1 negatively regulated the expression of miR-147, whereas miR-47 targeted PDPK1 to downregulate its expression. In radioprotection, TRT effectively upregulated NEAT1 to inhibit miR-147 and to upregulate PDPK1. We concluded that TRT could promote radioprotection by stimulating NEAT1 to upregulate PDPK1 expression by suppressing miR-147. NEAT1 could be a critical therapeutic target of radiation damage.

We discuss the contribution of right-handed neutrinos (RHNs) to the effective neutrino mass of the neutrinoless double beta decay within the minimal type-I seesaw model using the intrinsic seesaw relation of neutrino mass and mixing parameters and the relative mass dependence of the nuclear matrix elements. In the viable parameter space, we find the possibilities of both the enhancement and cancellation to the effective neutrino mass from RHNs. The bounds on the parameter space of the RHNs can be determined with the effective neutrino mass extracted from neutrinoless double beta decay experiments.

Dark matter (DM) direct detection experiments are entering the multiple-ton era and will be sensitive to the coherent elastic neutrino nucleus scattering (CEνNS) of solar neutrinos, enabling the possibility to explore contributions from new physics with light mediators at the low energy range. In this paper we consider light mediator models (scalar, vector and axial vector) and the corresponding contributions to the solar neutrino CEνNS process. Motivated by the current status of new generation of DM direct detection experiments and the future plan, we study the sensitivity of light mediators in DM direct detection experiments of different nuclear targets and detector techniques. The constraints from the latest 8B solar neutrino measurements of XENON-1T are also derived. Finally, we show that the solar neutrino CEνNS process can provide stringent limitation on the Lμ−Lτ model with the vector mediator mass below 100 MeV, covering the viable parameter space of the solution to the (g−2)μ anomaly.

Mercury (Hg) brings adverse effects to the environment and human beings and inorganic mercury (IHg) is a typical hepatic toxin. This work studied the impacts of IHg on gut microbes and metabolome together with its damage to liver and gut in rats through gut microbiome, metabolomics and metallomics. Sprague Dawley (SD) rats were orally exposed to 0.4 μg/mL IHg and sacrificed after 24 h. It was found that IHg perturbed greatly on the gut microbiota, such as increased pathogenic bacteria like G. bacillus. In addition, IHg also changed gut-liver axis related metabolites, which was confirmed by the secretion of a large number of inflammatory factors in both the gut and the liver. The changed gut-liver axis related metabolites correlated well to the changes of gut microbiome. In all, besides the direct deposition in liver of Hg, the perturbance to gut microbiome and alteration of gut-liver axis related metabolites by IHg also contributed to its hepatoxicity, which provides new insights about the hepatoxicity of chemicals. The strategy applied in this work may also be used to understand the hepatoxicity of other chemicals.

Cadmium (Cd) contamination in paddy fields is a serious health concern because of its high toxicity and widespread pollution. Recently, much progress has been made in elucidating the mechanisms involved in Cd uptake, transport, and transformation from paddy soils to rice grains, aiming to mitigate the associated health risk; however, these topics have not been critically reviewed to date. Here, we summarized and reviewed the (1) geochemical distribution and speciation of Cd in soil-rice systems, (2) mobilization, uptake, and transport of Cd from soil to rice grains and the associated health risks, (3) pathways and transformation mechanisms of Cd from soil to rice grains, (4) transporters involved in reducing Cd uptake, transport, and accumulation in rice plants, (5) factors governing Cd bioavailability in paddy, and (6) comparison of remediation approaches for mitigating the environmental and health risks of Cd contamination in paddy fields. Briefly, this review presents the state of the art about the fate of Cd in paddy fields and its transport from soil to grains, contributing to a better understanding of the environmental hazards of Cd in rice ecosystems. Challenges and perspectives for controlling Cd risks in rice are thus raised. The summarized findings in this review may help to develop innovative and applicable methods for controlling Cd accumulation in rice grains and sustainably manage Cd-contaminated paddy fields.

The terpene-conjugated curcuminoid bisabolocurcumin ether (BCE) is a newly identified bioactive curcuminoid, but its abundance in different Curcuma species is unknown. We developed an efficient MCI-gel-based method to purify BCE from C. longa, and established BCE fragmentation pathways under ESI-MS/MS. The abundances of BCE curcumin, demethoxycurcumin, and bisdemethoxycurcumin determined in C. longa rhizomes from Thailand, Indonesia, and China, C. longa roots from China, and C. phaeocaulis rhizomes from China. The abundance of the four compounds varied significantly, not only among different Curcuma species and cultivation regions, but also among different parts of the same species. BCEs were only detected in C. longa from Thailand and China, and in C. longa roots. C. longa from Thailand showed the highest abundance of curcuminoid [average 85.07 mg/g] and BCE [average 0.64 mg/g]. Moreover, BCE and three curcuminoids showed anti-inflammatory potential, as evidenced by the inhibition of lipopolysaccharide-induced production of nitric oxide in macrophages.

Background: Phthalates, which are used as excipients of drugs, have been related to adverse reproductive outcomes. However, the relationships between medication use and phthalate exposure among women undergoing in vitro fertilization (IVF) have not been studied. Objective: To investigate the associations between the medication intake and phthalate metabolites in urine and follicular fluid (FF). Method: Eight phthalate metabolites were measured in urine and FF samples from 274 women undergoing IVF using liquid chromatography-tandem mass spectrometry. Information on recent medication intake was obtained via interview by trained staff. We constructed generalized linear regression models to examine the associations of medication intake with phthalate metabolite concentrations and dose-response relationships between the number of medicines used and metabolite concentrations in two matrices. Results: Four of 10 drugs were used by more than 10% of the participants, including vitamins (23.0%), traditional Chinese medicine (TCM, 22.3%), antioxidants (12.4%) and amoxicillin (10.2%). Participants who had used TCM had 26.0% (95% CI: 0.0, 58.8%), 32.6% (95% CI: 4.2, 68.8%) and 32.3% (95% CI: 2.6, 70.6%) higher urinary mono-n-butyl phthalate (MBP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) concentrations, respectively, than those who had not. Antioxidant intake was associated with a 30.6% (95% CI: −48.5, −6.6%) decrease in the urinary MBP concentration. Compared with non-users, women who reported the use of medicines had 53.2% (95% CI: 2.7, 128.5%) higher concentrations of MMP and a 37.7% (95% CI: −60.7, −1.5%) lower level of MBP in FF, respectively. Conclusion: Our data suggest that the intake of some medications may increase phthalate exposure among women undergoing IVF.

New ab initio calculations of the isotopic reactor antineutrino fluxes are provided with exact numerical calculations of the lepton wave functions, assuming all the decay branches are allowed GT transitions. We illustrate that the analytical Fermi function and finite size effect each could have the largest spectral deviation of O(10%), whereas the effect of their combination could result in spectral deviations at the level of 5%—10%. Meanwhile, we also find that several forms of the extended charge distributions have negligible effects on the spectral variation. Using the state-of-the-art nuclear databases, compared to usual ab initio calculations using the analytical single beta decay spectrum, our new calculation shows sizable but opposite spectral deviations at the level of 2%—4% for the cumulative antineutrino and electron energy spectra which may partially contribute to the observed spectral excess in the high energy antineutrino range. Finally we observe that the bias of analytical beta decay spectrum approximation is rather universal for all the four fissionable isotopes.

Mercury (Hg) is one of the most toxic heavy metals. It can migrate around the globe and magnify through the food chain, ultimately harming human health. Urinary Hg reflects recent exposure of Hg, which reflects the status of environmental contamination by Hg. This review summarized the levels and presented temporal trends of urinary Hg in Chinese people (both the general public and the occupationally exposed people) reported from 1970s to 2010s. It was found that urinary Hg levels in 92.3% of the reported population were less than the reference value (10.0 µg/L) recommended by Chinese health authority, while 76.9% were less than the reference value (4.0 µg/L) recommended by World Health Organization (WHO) in the general public in China. For the temporal trend from 1970s to 2010s, the urinary Hg levels in the general public in China were found to decrease gradually. In the occupationally exposed people, the urinary Hg levels generally exceeded the reference value (10.0 µg/L) for the general public, and about half of them were higher than the occupational exposure limit (35.0 µg/g creatinine) set by Chinese Occupational Health Standard (WS/T 265 - 2006). From 1970s to 2010s, the urinary Hg levels in occupationally exposed population increased first and then decreased slowly. Hg miners in Guizhou were found to have the highest urinary Hg levels, while workers in Anhui, Chongqing, Qinghai and Shanxi also had high levels of urinary Hg. In all, the urinary Hg levels in both the general public and the occupationally exposed people decreased from 1970s to 2010s, especially in recent decades. Attention should be paid to occupationally exposed people since high levels of urinary Hg were found in them. The message provided in this review can help better understand the situation of Hg burden in Chinese people and lay a basis for the coming effectiveness evaluation on the implementation of Minamata Convention on Mercury.Capsule abstract: The urinary Hg levels in both the general public and the occupationally exposed people in China are decreasing.

Objective: This study aimed to evaluate the reliability and validity of the Chinese version of the Fear of Hypoglycemia scale with 15 items (FH-15). Methods: After obtaining the original author's authorization, the English version of the FH-15 scale was translated, back translated, and culturally debugged to obtain the Chinese version of FH-15. A convenient sampling method was used to extract patients with type 2 diabetes from four tertiary hospitals in Tianjin. A total of 408 patients with type 2 diabetes were investigated in the hospital to test the reliability and validity of Chinese version FH-15 scale. Results: The content validity index of the scale was 0.92, and the content validity index of each item was 0.8–1.0. The exploratory factor analysis extracted three common factors (fear, avoidance, and interference), which contained 15 items, and the cumulative variance contribution rate was 71.245%. The confirmatory factor analysis results showed that the model fit was better at 1.981 χ2/df, GFI = 0.901, CGI = 0.962, TLI = 0.952, and RMSEA = 0.070. The cut-off value for the total hypoglycemia fear scale was 30.5. The Cronbach's α coefficient of the three dimensions of the scale was 0.918, the Cronbach's α coefficient of each dimension is 0.876–0.916, the test–retest reliability was 0.903, and the test–retest reliability of each factor was 0.733–0.930. Conclusion: The Chinese version of the FH-15 scale can be considered reliable and valid. The item expression is concise, clear, and easy to understand. It is suitable for clinical practice as an initial screening tool to identify and evaluate the severity of fear of hypoglycemia in patients with type 2 diabetes. Keywords: Diabetes mellitus, Type 2, Fear, Hypoglycemia, Reliability, Validity

If finite but tiny masses of the three active neutrinos are generated via the canonical seesaw mechanism with three heavy sterile neutrinos, the 3×3 Pontecorvo–Maki–Nakagawa–Sakata neutrino mixing matrix V will not be exactly unitary. This kind of indirect unitarity violation can be probed in a precision reactor antineutrino oscillation experiment, but it may be entangled with terrestrial matter effects as both of them are very small. We calculate the probability of ν‾e→ν‾e oscillations in a good analytical approximation, and find that, besides the zero-distance effect, the effect of unitarity violation is always smaller than matter effects, and their entanglement does not appear until the next-to-leading-order oscillating terms are taken into account. Given a 20-kiloton JUNO-like liquid scintillator detector, we reaffirm that terrestrial matter effects should not be neglected but indirect unitarity violation makes no difference, and demonstrate that the experimental sensitivities to the neutrino mass ordering and a precision measurement of θ12 and Δ21≡m22−m12 are robust.

The possible existence of light and heavy sterile neutrinos may give rise to direct and indirect unitarity violation of the 3×3 lepton mixing matrix respectively. In the current work we study the potential of future accelerator neutrino facilities in probing the unitarity violation effects. Taking DUNE, T2HK and a low-energy Neutrino Factory (LENF) as working examples of future accelerator neutrino facilities, we study the distinct effects of direct and indirect unitarity violation on the discovery reach of the leptonic CP violation and precision measurements of θ23 in the three neutrino framework. In addition, constraints on the additional mixing parameters of direct and indirect unitarity violation are also discussed. Finally, we stress that the combination of experiments with different oscillation channels, different neutrino beams and different detector techniques will be an effective solution to the parameter degeneracy problem and give the robust measurement of leptonic CP violation even if the direct and indirect unitarity violation are taken into account.

We report the neutrino mass hierarchy (MH) determination of medium baseline reactor neutrino experiments with multiple detectors, where the sensitivity of measuring the MH can be significantly improved by adding a near detector. Then the impact of the baseline and target mass of the near detector on the combined MH sensitivity has been studied thoroughly. The optimal selections of the baseline and target mass of the near detector are ∼12.5 km and ∼4 kton respectively for a far detector with the target mass of 20 kton and the baseline of 52.5 km. As typical examples of future medium baseline reactor neutrino experiments, the optimal location and target mass of the near detector are selected for the specific configurations of JUNO and RENO-50. Finally, we discuss distinct effects of the reactor antineutrino energy spectrum uncertainty for setups of a single detector and double detectors, which indicate that the spectrum uncertainty can be well constrained in the presence of the near detector.

We discuss reactor antineutrino oscillations with non-standard interactions (NSIs) at the neutrino production and detection processes. The neutrino oscillation probability is calculated with a parametrization of the NSI parameters by splitting them into the averages and differences of the production and detection processes respectively. The average parts induce constant shifts of the neutrino mixing angles from their true values, and the difference parts can generate the energy (and baseline) dependent corrections to the initial mass-squared differences. We stress that only the shifts of mass-squared differences are measurable in reactor antineutrino experiments. Taking Jiangmen Underground Neutrino Observatory (JUNO) as an example, we analyze how NSIs influence the standard neutrino measurements and to what extent we can constrain the NSI parameters.

Sound waves technology has been applied to different plants. It has been found that sound waves were at different frequencies, sound pressure levels (SPLs), exposure periods, and distances from the source of sound influence plant growth. Experiments have been conducted in the open field and under greenhouse growing conditions with different levels of audible sound frequencies and sound pressure levels. Sound waves at 1 kHz and 100 dB for 1 h within a distance of 0.20 m could significantly promote the division and cell wall fluidity of callus cells and also significantly enhance the activity of protective enzymes and endogenous hormones. Sound waves stimulation could increase the plant plasma-membrane H+-ATPase activity, the contents of soluble sugar, soluble protein, and amylase activity of callus. Moreover, sound waves could increase the content of RNA and the level of transcription. Stress-induced genes could switch on under sound stimulation. Sound waves at 0.1–1 kHz and SPL of (70±5) dB for 3 h from plant acoustic frequency technology (PAFT) generator within a distance ranged from 30 to 60 m every other day significantly increased the yield of sweet pepper, cucumber and tomato by 30.05, 37.1 and 13.2%, respectively. Furthermore, the yield of lettuce, spinach, cotton, rice, and wheat were increased by 19.6, 22.7, 11.4, 5.7, and 17.0%, respectively. Sound waves may also strengthen plant immune systems. It has been proved that spider mite, aphids, gray mold, late blight and virus disease of tomatoes in the greenhouses decreased by 6.0, 8.0, 9.0, 11.0, and 8.0%, respectively, and the sheath blight of rice was reduced by 50%. This paper provides an overview of literature for the effects of sound waves on various growth parameters of plant at different growth stages.

Objective: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). Methods: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. Results: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. Conclusion: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection. Keywords: Dendritic cells, Apoptosis, Epstein-Barr virus infections

OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). METHODS: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. CONCLUSION: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.

Objective: To investigate the characteristics of three-dimensional distribution of subchondral fracture lines on the surface of the osteonecrosis femoral head, and to discuss the underlying mechanisms that contribute to its collapse. Methods: We retrospectively analyzed computed tomography (CT) images from 75 patients (comprising a total of 77 femoral heads) diagnosed with Association Research Circulation Osseous (ARCO) stage IIIA or IIIB femoral head necrosis. The three-dimensional structures of both the femoral head and the subchondral fracture line were reconstructed and subsequently fitted into normal femoral head model. A heat map of fracture line was generated to visualize its spatial distribution across the femoral heads surface.to observe its distribution. In addition to that, the femoral head was partitioned into four zones, and the frequency of each fracture line traversing different zones was calculated and analysed. Results: Highest and lowest density of subchondral fracture lines was demonstrated in anterolateral and posterolateral zone respectively. and most sparse in posterolateral. Furthermore, the three-dimensional heat map of fracture lines highlighted their most frequent occurrence in the anterolateral area, particularly near the junction of the femoral head and neck. One fracture line may pass through multiple areas, passage frequencies for fracture lines was observed in zones I, II, III and IV for 66 times (85.7 %), 52 times (67.5 %), 25 times (32.5 %) and 46 times (59.7 %), respectively, with a significant difference between zone I and other zones (P

Background: There is currently no well-accepted consensus on the association between gut microbiota and the response to treatment of immune checkpoint inhibitors (ICIs) in patients with advanced cancer. Methods: Fecal samples were collected before ICI treatment. Gut microbiota was analyzed using 16 S ribosomal RNA sequencing. We investigated the relationship between the α-diversity of fecal microbiota and patients’ clinical outcomes. Microbiota profiles from patients and healthy controls were determined. Pre-treatment serum was examined by cytokine array. Results: We analyzed 74 patients, including 42 with melanoma, 8 with kidney cancer, 13 with lung cancer, and 11 with other cancers. Combination therapy of anti-PD1 and anti-CTLA-4 was used in 14 patients, and monotherapy in the rest. Clinical benefit was observed in 35 (47.3 %) cases, including 2 complete responses, 16 partial responses, and 17 stable diseases according to RECIST criteria. No significant difference in α-diversity was found between the benefiter and non-benefiter groups. However, patients with α-diversity within the range of our healthy control had a significantly longer median overall survival (18.9 months), compared to the abnormal group (8.2 months) (p = 0.041, hazard ratio = 0.546) for all patients. The microbiota composition of the benefiters was similar to that of healthy individuals. Furthermore, specific bacteria, such as Prevotella copri and Faecalibacterium prausnitzii, were associated with a favorable outcome. We also observed that serum IL-18 before treatment was significantly lower in the benefiters, compared to non-benefiters. Conclusions: The α-diversity of gut microbiota is positively correlated with more prolonged overall survival in cancer patients following ICI therapy.

Background/Purpose: Multimorbidity is a worldwide issue when aging is rapidly. The aim of this study was to evaluate the impact of demography, morbidity, disability and depression on short-term and long-term mortality for multimorbid inpatients. Methods: The participants’ information were assessed upon recruitment. Multimorbidity and disability were measured by modified Charlson comorbidities Index (CCI) and Barthel Index for Activity of Daily Living (ADL), respectively. Depression was screened over one-item self-reported perceptions of depressed mood rated as yes or no. The factors of in-hospital mortality and periodic mortality after discharge were examined by Cox proportional hazard regression and Kaplan–Meier survival analyses. Results: A total of 201 inpatients from a hospitalist's ward were recruited. The in-hospital mortality was 14.4%, while 24-month mortality was 57.8%. After adjustment, severe ADL dependence (

Lung adenocarcinoma (LUAD), the most common histological type of non-small cell lung cancer, is one of the most malignant and deadly diseases. Current treatments for advanced LUAD patients are far from ideal and require further improvements. Here, we utilized a systematic integrative analysis of LUAD microRNA sequencing (miRNA-seq) and RNA-seq data from The Cancer Genome Atlas (TCGA) to identify clinically relevant tumor suppressor miRNAs. Three miRNA candidates (miR-195-5p, miR-101-3p, and miR-338-5p) were identified based on their differential expressions, survival significance levels, correlations with targets, and an additive effect on survival among them. We further evaluated mimics of the three miRNAs to determine their therapeutic potential in inhibiting cancer progression. The results showed not only that each of the miRNA mimics alone but also the three miRNA mimics in combination were efficient at inhibiting tumor growth and progression with equal final concentrations, meaning that the three miRNA mimics in combination were more effective than the single miRNA mimics. Moreover, the combined miRNA mimics provided significant therapeutic effects in terms of reduced tumor volume and metastasis nodules in lung tumor animal models. Hence, our findings show the potential of using the three miRNAs in combination to treat LUAD patients with poor survival outcomes.

Risk and prognostic factors for acute kidney injury (AKI) have been published in various studies across various populations. We aimed to explore recent advancements in and provide updated recommendations on AKI risk stratification and information about local AKI risk factors. The Taiwan Acute Kidney Injury Task Force reviewed relevant recently published literature and reached a consensus after group meetings. Systemic review and group discussion were performed. We conducted a meta-analysis according to the PRISMA statement for evaluating the diagnostic performance of the furosemide stress test. Several risk and susceptibility factors were identified through literature review. Contrast-associated AKI prediction models after coronary angiography were one of the most discussed prediction models we found. The basic approach and evaluation of patients with AKI was also discussed. Our meta-analysis found that the furosemide stress test can be used as a prognostic tool for AKI progression and to identify patients with AKI who are at low risk of renal replacement therapy. Factors associated with de novo chronic kidney injury or renal non-recovery after AKI were identified and summarized. Our review provided practical information about early identification of patients at high risk of AKI or disease progression for Taiwan local clinics.

Colorectal cancer (CRC) results from the uncontrolled growth of cells in the colon, rectum, or appendix. The 5-year relative survival rate for patients with CRC is 65% and is correlated with the stage at diagnosis (being 91% for stage I at diagnosis versus 12% for stage IV). This study aimed to identify CRC driver genes to assist in the design of a cancer panel to detect gene mutations during clinical early-stage screening and identify genes for use in prognostic assessments and the evaluation of appropriate treatment options. First, we utilized bioinformatics approaches to analyze 354 paired sequencing profiles from The Cancer Genome Atlas (TCGA) to identify CRC driver genes and analyzed the sequencing profiles of 38 patients with >5 years of follow-up data to search for prognostic genes. The results revealed eight driver genes and ten prognostic genes. Next, the presence of the identified gene mutations was verified using tissue and blood samples from Taiwanese CRC patients. The results showed that the set identified gene mutations provide high coverage for driver gene screening, and APC, TP53, PIK3CA, and FAT4 could be detected in blood as ctDNA test targets. We further found that BCL7A gene mutation was correlated with prognosis in CRC (log-rank p-value = 0.02), and that mutations of BCL7A could be identified in ctDNA samples. These findings may be of value in clinical early cancer detection, disease monitoring, drug development, and treatment efforts in the future.

Copper nanoclusters (Cu NCs) with a core size smaller than 2 nm exhibit fascinating physical and chemical properties, bridging between nanoparticles and atomic/molecular structures. In particular, the unique fluorescence (FL) characteristics of Cu NCs have attracted increasingly attention in the past decade. Compared with gold or silver NCs, Cu is a relatively cheap, abundant and readily available element, which makes Cu NCs more attractive to the development of sensors. However, Cu NCs still face serious issues, such as low quantum yield and easy to oxidation. This review discusses the latest developments in Cu NCs, with particular emphasis on their synthesis, optical properties, and applications in monitoring water quality. Pivotal factors that control the stability and FL properties of Cu NCs are emphasized. Examples of Cu NCs for monitoring of pH values and sensing of various analytes such as Hg2+, NO2−, S2−, I−, and 2,4,6-trinitrotoluene are provided to show their sensing mechanisms, advantages, and disadvantages. Possible strategies for overcoming the low quantum yields and small scales of preparation of Cu NCs are suggested. To make Cu NCs more popular for sensing, we suggest that Cu NCs shall be integrated with portable microsystems such as array and microfluidic devices.

Summary: The bone marrow niche plays a critical role in controlling the fate of hematopoietic stem cells (HSCs) by integrating intrinsic and extrinsic signals. However, the molecular events in the HSC niche remain to be investigated. Here, we report that intercellular adhesion molecule-1 (ICAM-1) maintains HSC quiescence and repopulation capacity in the niche. ICAM-1-deficient mice (ICAM-1−/−) displayed significant expansion of phenotypic long-term HSCs with impaired quiescence, as well as favoring myeloid cell expansion. ICAM-1-deficient HSCs presented normal reconstitution capacity during serial transplantation; however, reciprocal transplantation experiments showed that ICAM-1 deficiency in the niche impaired HSC quiescence and repopulation capacity. In addition, ICAM-1 deletion caused failure to retain HSCs in the bone marrow and changed the expression profile of stroma cell-derived factors, possibly representing the mechanism for defective HSCs in ICAM-1−/− mice. Collectively, these observations identify ICAM-1 as a regulator in the bone marrow niche. : In this article, Jie Zhou and colleagues show that ICAM-1 expression in bone marrow niche contributes to the quiescence and repopulation capacity of HSCs. ICAM-1 deficiency changes the expression profile of stroma-derived factors, thus causing failure of HSC retention in the bone marrow. Clinical data indicate that ICAM-1 might participate in the progression of myelocytic leukemia. Keywords: hematopoietic stem cells, homeostasis, intercellular adhesion molecule-1, bone marrow niche

Emergency department (ED) overcrowding is a universal problem, especially with the shortage of hospital beds. We studied the characteristics and outcomes of patients with prolonged ED stays, which has rarely been studied before. Methods: We conducted a retrospective study at a tertiary medical center in Taiwan. Prolonged stay in the ED was defined as a stay of more than 72 hours in the ED before admission. The medical records were reviewed for data analysis. Results: From November 1, 2009 to January 31, 2010, a total of 1364 general medical patients were enrolled. The mean age was 66.4 ± 17.8 years, with 53.4% male. The mean Charlson Comorbidity Index (CCI) was 3.0 ± 3.1. The mean length of ED stay was 43.9 ± 41.0 hours. The CCI (4.1 ± 3.5 vs. 2.8 ± 3.0, p

Patients with end-stage renal disease (ESRD) are at particular risk for methicillin-resistant Staphylococcus aureus (MRSA) infections, especially via nasal colonization of MRSA. Surveillance cultures are recommended to identify patients colonized by MRSA. Methods: Clinical data and screening cultures of S. aureus from the anterior nares of 541 patients on long-term dialysis in the hospitals were performed in March 2007. The follow-up survey was conducted 1 year later. Results: A total of 32 (5.9%) of the 541 patients were positive nasal cultures for MRSA, while 89 (16.5%) were positive for methicillin-susceptible S. aureus (MSSA). In a multivariate analysis, risk factors for ESRD patients with MRSA colonization included congestive heart failure, nursing home admission, and nasogastric tube feeding in the last 3 months. Follow-up of the 32 MRSA colonized patients showed that one (3.1%) died due to MSSA and three (9.3%) died due from MRSA infection. Conclusions: We found that patients with ESRD and MRSA nasal colonization were associated with a history of congestive heart failure, nursing home admission, and nasogastric tube feeding in the last 3 months.

Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. Methods: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. Results: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). Conclusion: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism.