China's Modified Version of Sniffin' Sticks 12-Identification Test Used in Chinese Parkinson's Disease and Multiple System Patients: Comparison of Three Olfactory Testing Methods.

Objectives: The aim of this study was to compare the Sniffin' Sticks 12-identification test (SIT-12), China-modified version of the SIT-12 test (Ch-SIT-12) and brief smell identification test for Chinese (B-SITC) in Chinese population of Parkinson's disease (PD) and multiple system atrophy (MSA). Methods: 36 patients with PD and 7 patients with MSA were enrolled in this study. Three olfactory testing methods (SIT-12, Ch-SIT-12, and B-SITC) were used to test the olfactory function in all participants. Furthermore, demographic and clinical data were collected. Results: There was no significant difference between three olfactory tests in patients with PD (B-SITC vs. SIT-12: P=0.508; Ch-SIT-12 vs. B-SITC: P=0.146; and SIT-12 vs. Ch-SIT-12: P=0.375). Tremor-dominant (TD) subtypes have better olfactory function than akinetic-rigid dominant (ARD) subtypes when using Ch-SIT-12 (77.8% vs. 29.6%, P=0.019) or B-SITC (55.6% vs. 14.8%, P=0.026). There was a statistical difference between the PD and MSA using Ch-SIT-12 to test the olfactory function (P=0.046). Conclusions: Our results indicated that SIT-12, Ch-SIT-12 and B-SITC can be used for the detection of olfactory dysfunction in Chinese population of PD. TD subtypes may have better olfactory function than ARD subtypes. In addition, Ch-SIT-12 may be used to differentiate PD from MSA, but that should be confirmed in a larger population.

Risk factors and prediction model for mortality in HIV/Talaromyces marneffei co-infection: A retrospective cohort study.

Background: This study aimed to identify the risk factors associated with mortality among patients co-infected with human immunodeficiency virus (HIV) and Talaromyces marneffei (TM) in China, and develop a risk prediction model. Methods: In this retrospective cohort analysis conducted from 2013 to 2024, comprehensive clinical data from 160 patients were analyzed using a logistic regression model to identify mortality predictors and construct a predictive model. An additional 36 patients constituted the validation cohort, which was specifically designed to evaluate the predictive value of the model. Model performance was assessed using the area under the curve (AUC). Results: The overall mortality rate for hospitalized patients with HIV/TM co-infection was 17.35 %. The median age was 35.0 years, and 89.30 % were male. Additionally, 89.80 % of the patients reported fever and 87.76 % presented with lymphadenopathy. Key independent risk factors associated with mortality included age (odds ratio (OR): 1.103, 95 % confidence interval (CI) = 1.033-1.178, P = 0.003), procalcitonin (PCT) levels (OR: 1.270, 95 % CI = 1.052-1.534, P = 0.013), and urea to albumin ratio (UAR) (OR: 1.491, 95 % CI = 1.175-1.892, P < 0.001). Advanced age, elevated PCT levels, and increased UAR were identified as independent risk factors of mortality. Furthermore, the mortality prediction probability combining age, PCT, and UAR exhibited a high predictive value in patients with HIV/TM co-infection. Additionally, the AUC showed a good discrimination ability in the validation group (AUC, 0.898). Conclusions: Advanced age, elevated PCT levels, and increased UAR significantly determine mortality in patients with HIV/TM co-infection. These findings underscore the potential of using laboratory parameters as predictive indicators of mortality, facilitating the early identification of HIV/TM co-infection cases in clinical practice.

Correlative Super-resolution Optical and Electron Microscopic Imaging of Intracellular Ribosomal RNA by a Terpyridine Iridium(III) Complex.

Ribosomal RNA (rRNA) plays a vital role in binding amino acids together, which dictates the primary structure of a protein. Visualization of its intracellular distribution and dynamics during protein synthesis enables a better understanding of the correlated biological essence. However, appropriate tools targeting live cell rRNA that are capable of multimodal imaging at the nanoscale are still lacking. Here, we rationally designed a series of terpyridine ammonium iridium(III) complexes, one of which is capable of selectively labeling rRNA in living cells. Its metal core and photostable nature allow further super-resolution STED imaging of rRNA found on the rough endoplasmic reticulum at a ∼40 nm resolution that is well correlated under correlative light and electron microscopy (CLEM). Interestingly, the Ir(III) complex demonstrated rRNA dynamics in living cells while boosting protein synthesis at the nanoscale. Our work offers a versatile tool to visualize rRNA synchronously under optical and electron microscopy, which provides a better understanding of rRNA evolution in living systems.

Restricted and epitaxial growth of MnO2-x nano-flowers in/out carbon nanofibers for long-term cycling stability supercapacitor electrodes.

Carbon nanofibers (CFs) have been widely applied as electrodes for energy storage devices owing to the features of increased contact area between electrodes and electrolyte, and shortened transmission route of electrons. However, the poor electrochemical activity and severe waste of space hinder their further application as supercapacitors electrodes. In this work, MnO2-x nanoflowers restricted and epitaxial growth in/out carbon nanofibers (MnO2/MnO@CF) were prepared as excellent electrode materials for supercapacitors. With the synergistic effect of uniquely designed structure and the introduction of MnO and MnO2 nanoflowers, the prepared interconnected MnO2/MnO@CF electrodes demonstrated satisfactory electrochemical performance. Furthermore, the MnO2/MnO@CF//activated carbon (AC) asymmetric supercapacitor offered an outstanding long-term cycle stability. Besides, kinetic analysis of MnO2/MnO@CF-90 was conducted and the diffusion-dominated storage mechanism was well-revealed. This concept of "internal and external simultaneous decoration" with different valence states of manganese oxides was proven to improve the electrochemical performance of carbon nanofibers, which could be generalized to the preparation and performance improvement of other fiber-based electrodes.

Variation of adverse drug events in different settings in Africa: a systematic review.

BACKGROUND: Adverse drug events (ADEs) represent challenges affecting Africa's healthcare systems owing to the increased healthcare expenditure and negative health outcomes of ADEs. OBJECTIVES: We aimed to systematically review published studies on ADEs and synthesize the existing evidence of ADE prevalence in Africa. METHODS: Studies reporting on ADE occurrence in African settings and published from Jan 1, 2000 to Oct 1, 2023 were identified by searching PubMed, EBSCO, Science Direct, and Web of Science. Studies that either articulately investigated ADEs caused by clinical condition (such as HIV patients) or ADEs caused by exposure to specific drug(s) (such as antibiotics) were considered specific and the remaining were general. Grouped ADE prevalence rates were described using median and interquartile range (IQR). PROSPERO registration (CRD42022374095). RESULTS: We included 78 observational studies from 15 African countries that investigated the prevalence of ADEs leading to hospital admissions (17 studies), developed during hospitalizations (30 studies), and captured in the outpatient departments (38 studies) or communities (4 studies). Twelve studies included multiple settings. The median prevalence of ADE during hospitalization was 7.8% (IQR: 4.2-21.4%) and 74.2% (IQR: 54.1-90.7%) in general and specific patients, respectively. The ADE-related fatality rate was 0.1% and 1.3% in general and specific patients. The overall median prevalence of ADEs leading to hospital admissions was 6.0% (IQR: 1.5-9.0%); in general, patients and the median prevalence of ADEs in the outpatient and community settings were 22.9% (IQR: 14.6-56.1%) and 32.6% (IQR: 26.0-41.3%), respectively, with a median of 43.5% (IQR: 16.3-59.0%) and 12.4% (IQR: 7.1-28.1%) of ADEs being preventable in general and specific patients, respectively. CONCLUSIONS: The prevalence of ADEs was significant in both hospital and community settings in Africa. A high ADE prevalence was observed in specific patients, emphasizing important areas for improvement, particularly in at-risk patient groups (e.g., pediatrics, HIV, and TB patients) in various settings. Due to limited studies conducted in the community setting, future research in this setting is encouraged.

Body mass index and pressure injuries risk in hospitalized adult patients: A dose-response analysis.

BACKGROUND: The association between underweight and pressure injuries (PIs) has been established in several studies. However, there is a lack of well-designed research investigating the connection between overweight and obesity with these injuries. OBJECTIVE: This meta-analysis aims to investigate the dose-response relationship between body mass index (BMI) and the risk of PIs in adult hospitalized patients. METHODS: PubMed, Web of Science, and MEDLINE Databases were searched from inception to May 2024. Observational articles with at least three BMI categories were included in the study. BMI was defined as underweight, normal weight, overweight, and morbid obesity for the meta-analysis. The non-linear relationship between BMI and the risk of PIs in hospitalized adults was investigated using restricted cubic spline models. Fractional polynomial modeling was used. RESULTS: Eleven articles reporting at least 3 categories of BMI met the inclusion criteria, including 31,389 participants. Compared to patients with normal weight, those with underweight, obesity, and morbid obesity exhibited an increased risk of PIs, with odds ratios of 1.70 (95%CI:1.50-1.91), 1.12 (95%CI:1.02-1.24), 1.70 (95%CI:1.13-2.55), respectively. A J-shaped dose-response model was established for the relationship between PI risk and BMI (Pnon-linearity < 0.001, Plinearity = 0.745). CONCLUSION: The J-shaped dose-response pattern revealed that underweight, obesity and morbid obesity heightened the risk of PIs in hospitalized adults. Lower and higher BMI values may signify an increased risk for PIs, particularly among the elderly with lower BMI, providing valuable guidance for medical staff.

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To explore the temporal and spatial variations in phytoplankton community in small estuaries, we collected surface water samples from Yongjiang River estuary during wet, normal, and dry seasons and determined the main driving factors of phytoplankton community. A total of 358 species belonging to nine phyla and 123 genera were identified in all seasons. During wet, normal, and dry seasons, species number was 276, 154 and 151, and the abundance was (170.45±225.43)×103, (51.92±30.28)×103 and (31.65±12.79)×103 cells·L-1, respectively. Diatoms dominated the phytoplankton community, and the main dominant species were Cyclotella meneghiniana, Skeletonema costatum, and Paralia sulcata. Shannon diversity and Pielou evenness indices decreased from inside mouth to outside mouth in wet season, but there was no obvious spatial difference in normal season or dry season. Results of non-metric multidimensional scaling analysis and analysis of similarities showed that phytoplankton community composition differed significantly among different regions (inside, at and outside mouth) and different seasons. In wet season, phytoplankton abundance was significantly positively correlated with temperature, dissolved inorganic nitrogen, and dissolved reactive phosphorus, but significantly negatively correlated with salinity. In normal season, phytoplankton abundance was significantly negatively correlated with temperature. In dry season, it was not significantly correlated with environmental factors. Results of redundancy analysis showed that temperature, salinity, ammonium and dissolved reactive phosphorus explained the variations in phytoplankton community by 19.5%, 11.9%, 9.4% and 8.2%, respectively. These results revealed high dominance of diatoms and the main driving factors (temperature, salinity and nutrients) of phytoplankton community in Yongjiang River estuary.

Strand displacement-triggered FRET nanoprobe tracking TK1 mRNA in living cells for ratiometric fluorimetry of nucleic acid biomarker.

A precisely designed dual-color biosensor has realized a visual assessment of thymidine kinase 1 (TK1) mRNA in both living cells and cell lysates. The oligonucleotide probe is constructed by hybridizing the antisense strand of the target and two recognition sequences, in which FAM serves as the donor and TAMRA as the acceptor. Once interacting with the target, two recognition strands are replaced, and then the antisense complementary sequence forms a more stable double-stranded structure. Due to the increasing spatial distance between two dyes, the FRET is attenuated, leading to a rapid recovery of FAM fluorescence and a reduction of TAMRA fluorescence. A discernible color response from orange to green could be observed by the naked eye, with a limit of detection (LOD) of 0.38 nM and 5.22 nM for spectrometer- and smartphone-based assays, respectively. The proposed ratiometric method transcends previous reports in its capacities in visualizing TK1 expression toward reliable nucleic acid biomarker analysis, which might establish a general strategy for ratiometric biosensing via strand displacement.

A case report of pegcetacoplan use for a pregnant woman with paroxysmal nocturnal hemoglobinuria.

Background: Paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disease, is associated with high maternal and fetal mortality rates. Only 1 medication approved for PNH, the complement component 5 inhibitor eculizumab, has published evidence of use during pregnancy. Key Clinical Question: What were the circumstances and outcomes of the first use of pegcetacoplan, a complement component 3 inhibitor, by a pregnant woman with PNH? Clinical Approach: The patient, with a history of 2 miscarriages and a suboptimal response to eculizumab, had hematologic improvement after switching to pegcetacoplan. She continued pegcetacoplan throughout her pregnancy. At gestational week 30, she developed abruptio placentae and breakthrough hemolysis. She delivered a normal-appearing male infant via emergency cesarean section. The breakthrough hemolysis resolved quickly with short-term intensive pegcetacoplan dosing and add-on eculizumab. To date, her laboratory values remain normal, and she has had no thromboembolic events; her son has not demonstrated growth defects. Conclusion: This is the first report of pegcetacoplan treatment for PNH throughout pregnancy. The mother recovered promptly from breakthrough hemolysis that prompted an emergency delivery. Her son, who was born prematurely but healthy, has developed normally.

Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Characteristics and risk assessment of heavy metals in groundwater at a typical smelter-contaminated site in Southwest China.

To explore the characteristics and evaluate the risk of heavy metals in groundwater at a typical smelter-contaminated site, this study focuses on a representative a historical arsenic smelting plant in Southwest China, where the primary historical products were metallic arsenic (∼1000 tons/year) and arsenic trioxide (∼2000 ton/year). The results demonstrated As and Pb as the main pollutants in soil, and As and Cd as main pollutants in groundwater through soil profiling and quarterly groundwater analysis. The maximum As and Pb in the surface soil were 76800 and 2290 mg/kg, respectively, with As vertically infiltrating the deep gravel-sand layer (18-20 m). The groundwater pollution distribution progressively increased along flow direction, influenced by seasonal surface runoff and infiltration fluctuations. The groundwater pollutant concentrations during the dry season notably surpassed those during the wet season, with maximum As and Cd concentrations of 111.64 mg/L and 19.85 µg/L during the dry season, respectively. Furthermore, the analytic hierarchy process (AHP) was applied to evaluate the comprehensive risk of contaminated-site across pollution source load, regional groundwater intrinsic vulnerability, and evaluation of nearby sensitive receptors. The results revealed that the carcinogenic risk of lead in surface soil was moderate to high, while arsenic posed a high carcinogenic risk, contributing to an overall carcinogenic risk proportion of 89.6% in surface soil. Exposure through groundwater intake was identified as the primary pathway, with carcinogenic and noncarcinogenic risks exceeding those through skin contact. The final weights result demonstrated that the principal risk factors are the intrinsic arsenic load and protective target characteristics of regional groundwater at this site. This study provides a reference for comprehensive assessments of similarly contaminated industrial and smelting sites.

Identification of PSMD11 as a novel cuproptosis- and immune-related prognostic biomarker promoting lung adenocarcinoma progression.

BACKGROUND: Due to the unfavorable prognosis associated with lung adenocarcinoma (LUAD), the development of targeted therapies and immunotherapies is essential. Cuproptosis, an emerging form of regulated cell death, is implicated in mitochondrial metabolism and is induced by copper ions. This study aimed to explore the prognostic value of cuproptosis- and immune-related genes (CIRGs) in LUAD. METHODS: We used The Cancer Genome Atlas database to develop a prognostic prediction model for LUAD patients based on eight CIRGs. Using Cox regression analysis, we determined that the CIRG signature is a reliable, independent prognostic factor. We further identified PSMD11 as a critical CIRG and performed immunohistochemistry to study the protein expression levels of PSMD11 in LUAD tissues. We also investigated the impact of PSMD11 on the biological behavior of lung cancer cell lines. RESULTS: We found that patients with low PSMD11 expression levels displayed an improved prognosis compared with those with high PSMD11 expression levels. Overexpression of PSMD11 enhanced proliferation, migration, invasion, and tumor growth of lung carcinoma cell line A549, while PSMD11 knockdown diminished proliferation, migration, invasion, and tumor growth of lung carcinoma cell line PC9. Additionally, we discovered that PSMD11 expression was positively correlated with the infiltration of myeloid-derived suppressor cells and the increased expression of immunosuppressive molecules. CONCLUSION: These findings suggest that PSMD11 may serve as a valuable prognostic biomarker and therapeutic target for LUAD.

Unraveling the mechanism of thermotolerance by Set302 in Cryptococcus neoformans.

The underlying mechanism of thermotolerance, which is a key virulence factor essential for pathogenic fungi such as Cryptococcus neoformans, is largely unexplored. In this study, our findings suggest that Set302, a homolog of Set3 and a subunit of histone deacetylase complex Set3C, contributes to thermotolerance in C. neoformans. Specifically, the deletion of the predicted Set3C core subunit, Set302, resulted in further reduction in the growth of C. neoformans at 39°C, and survival of transient incubation at 50°C. Transcriptomics analysis revealed that the expression levels of numerous heat stress-responsive genes altered at both 30°C and 39°C due to the lack of Set302. Notably, at 39°C, the absence of Set302 led to the downregulation of gene expression related to the ubiquitin-proteasome system (UPS). Based on the GFP-α-synuclein overexpression model to characterize misfolded proteins, we observed a pronounced accumulation of misfolded GFP-α-synuclein at 39°C, consequently inhibiting C. neoformans thermotolerance. Furthermore, the loss of Set302 exacerbated the accumulation of misfolded GFP-α-synuclein during heat stress. Interestingly, the set302∆ strain exhibited a similar phenotype under proteasome stress as it did at 39°C. Moreover, the absence of Set302 led to reduced production of capsule and melanin. set302∆ strain also displayed significantly reduced pathogenicity and colonization ability compared to the wild-type strain in the murine infection model. Collectively, our findings suggest that Set302 modulates thermotolerance by affecting the degradation of misfolded proteins and multiple virulence factors to mediate the pathogenicity of C. neoformans.IMPORTANCECryptococcus neoformans is a pathogenic fungus that poses a potential and significant threat to public health. Thermotolerance plays a crucial role in the wide distribution in natural environments and host colonization of this fungus. Herein, Set302, a critical core subunit for the integrity of histone deacetylase complex Set3C and widely distributed in various fungi and mammals, governs thermotolerance and affects survival at extreme temperatures as well as the formation of capsule and melanin in C. neoformans. Additionally, Set302 participates in regulating the expression of multiple genes associated with the ubiquitin-proteasome system (UPS). By eliminating misfolded proteins under heat stress, Set302 significantly contributes to the thermotolerance of C. neoformans. Moreover, Set302 regulates the pathogenicity and colonization ability of C. neoformans in a murine model. Overall, this study provides new insight into the mechanism of thermotolerance in C. neoformans.

Interactions Between Endogenous Opioids and the Immune System.

The endogenous opioid system, which consists of opioid receptors and their ligands, is widely expressed in the nervous system and also found in the immune system. As a part of the body's defense machinery, the immune system is heavily regulated by endogenous opioid peptides. Many types of immune cells, including macrophages, dendritic cells, neutrophils, and lymphocytes are influenced by endogenous opioids, which affect cell activation, differentiation, proliferation, apoptosis, phagocytosis, and cytokine production. Additionally, immune cells also synthesize and secrete endogenous opioid peptides and participate peripheral analgesia. This chapter is structured into two sections. Part one focuses on immunoregulatory functions of central endogenous opioids; and part two describes how opioid peptide-containing immune cells participate in local analgesia.

Ultra-slow-light and dynamically quantitative optical storage modulation via quasi-BICs.

We achieve dynamically tunable dual quasi-bound states in the continuum (quasi-BICs) by implementing them in a silicon-graphene multilayer composite structure and utilize the quasi-BIC modes to achieve ultra-large group delays (velocity of light slows down 105 times), showing 2-3 orders of magnitude higher than the group delays of previous electromagnetically induced transparency modes. The double-layer graphene holds great tuning capability and leads to the dramatically reduced group delay from 1929.82 to 1.58 ps with only 100 meV. In addition, the log-linear variation rule of group delay with Fermi level (Ef) in the range of 0-10 meV is analyzed in detail, and the double-logarithmic function relationship between the group delay and quality factor (Q-factor) is theoretically verified. Finally, the quantitative modulation of the optical storage is further realized in this basis. Our research provides ideas for the reform and upgrading of slow optical devices.

Loss-of-Function Thr347Ala Variant in the G Protein Subunit-α11 Causes Familial Hypocalciuric Hypercalcemia 2 (FHH2).

CONTEXT AND OBJECTIVES: To date, only four loss-of-function variants in the GNA11 gene encoding the G protein subunit α11 (Gα11) leading to familial hypocalciuric hypercalcemia 2 (FHH2) have been characterized. Gα11 is involved in calcium-sensing receptor (CaSR) signaling, and loss-of-function variants in GNA11 lead to reduced agonist potency at CaSR and an FHH phenotype. DESIGN AND PARTICIPANTS: We have identified a family with a heterozygous GNA11 Thr347Ala variant and characterized its impact on calcium homeostasis in FHH2 patients and the signaling properties of CaSR through the Gα11-Thr347Ala variant in vitro. MAIN OUTCOME MEASURES: The index patient and her family had clinical, biochemical, and genetic analyses performed. The expression levels of Gα11 and the cell-surface expression levels of CaSR in human embryonic kidney 293A Gq/11 knock-out cells (ΔGq/11-HEK293A) co-transfected with CaSR and Gα11 (wild type (WT) or Thr347Ala) were determined, and the functional properties exhibited by calcium at CaSR were characterized in an inositol monophosphate (IP1) accumulation assay. RESULTS: Heterozygous carriers of the GNA11 Thr347Ala variant had mild asymptomatic hypercalcemia, hypocalciuria, and inappropriately high normal parathyroid hormone (PTH) levels considering their elevated serum calcium levels. Whereas the variant did not impact Gα11 expression or CaSR cell surface expression levels, calcium displayed a moderately but significantly lower agonist potency at CaSR/Gα11-Thr347Ala-transfected cells compared with CaSR/Gα11-WT-transfected cells in the IP1 accumulation assay (EC50 values of 5.67 mM and 4.38 mM, respectively). CONCLUSIONS: This identification of a novel GNA11 variant causing FHH2 substantiates the important role of Gα11 for CaSR signaling and Ca2+ homeostasis.

Interplay between Wnt signaling molecules and exosomal miRNAs in breast cancer (Review).

Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial­mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.