Early smoking lead to worse prognosis of COPD patients: a real world study.

BACKGROUND: Smoking remains a major risk factor for the development and progression of chronic obstructive pulmonary disease (COPD). Due to the adolescent smoking associated with worse health state, the age, at which an individual started smoking, might play a key role in shaping the trajectory of COPD development and the severity. METHODS: We conducted an observational study from September 2016 through January 2023 of eligible patients hospitalized with COPD. Patients who started smoking during the alveolar development stage (ADS, smoking initiation ≤ 24 years old) were defined as early smoking patients, and patients who started smoking after ADS (smoking initiation > 24 years old) were defined as late smoking patients. We collected demographic and clinical data characterizing the patients and documented their condition from hospital discharge to follow-up. The primary endpoints were short-term (within one year), 3-year, and long-term (beyond 3 years) all-cause mortality after discharge. RESULTS: Among 697 COPD patients, early smoking patients had a lower smoking cessation rate (P < 0.001) and a higher smoking index (P < 0.001) than late smoking patients. Although adjusted smoking index, early smoking patients still had poorer lung function (P = 0.023), thicker left ventricular diameters (P = 0.003), higher frequency of triple therapy use during stable stage (P = 0.049), and more acute exacerbations in the past year before enrollment (P < 0.05). Survival analysis showed that they had a higher risk of death after discharge within three years (P = 0.004) and beyond three years (P < 0.001). Furthermore, even in early smoking COPD patients who quit smoking after adjusting the smoking index had poorer lung function (P < 0.05) and thicker left ventricular diameters (P = 0.003), and survival analysis also showed that they had a higher long-term mortality rate (P = 0.010) and shorter survival time (P = 0.0128). CONCLUSION: Early smoking COPD patients exhibited multiple adverse clinical outcomes, including heavy cigarette addiction, compromised pulmonary function, augmented left ventricular diameter, and elevated mortality risk. Additional, smoking cessation could not bring enough improvement of health state in early smoking COPD patients as late smoking COPD patients. Consequently, early intervention and specialized cessation approaches for younger smokers are of paramount importance in this context.

Errors and Adherence to Inhaled Medications in Chinese Adults with COPD.

BACKGROUND: Adherence to inhaled medications is key to chronic obstructive pulmonary disease (COPD) control and management. OBJECTIVE: To assess errors and adherence to inhalation therapy in COPD patients, and identify potential factors associated with poor adherence. METHODS: This cross-sectional study was conducted from October 1, 2022, to November 30, 2022, in 24 hospital outpatient departments in different cities of Hunan Province, China. Adherence to inhaled medications was measured using the 10-item Test of Adherence Inventory, and the results were expressed using both descriptive and inferential statistics. RESULTS: A total of 2218 clinically confirmed adult COPD patients completed the questionnaires, and 1423 patients with more than a 3-month history of inhalation therapy were analyzed. This study found that 61.3% of patients made one or more use errors. Not holding the breath after inhalation or holding the breath for less than 3 s had the highest reporting rate (30.7%). A considerable proportion of patients (66.6%) demonstrated suboptimal adherence to inhaled medications. Patients who resided in rural areas (OR 1.45, 95% CI 1.12-1.88), used dual therapy (OR 1.47, 95% CI 1.05-2.05), and exhibited common use errors (OR 3.02, 95% CI 2.39-3.82) were more likely to present suboptimal adherence. Patients with CAT (Chronic Obstructive Pulmonary Disease Assessment Test) score < 10 (OR 0.73, 95% CI 0.56-0.94), a junior high school education and above (OR 0.73, 95% CI 0.57-0.94), and duration of inhaled medication use > 3 years (OR 0.63, 95% CI 0.47-0.83) were associated with better adherence. CONCLUSION: Suboptimal adherence to inhaled medications and many inhalation therapy errors were identified among COPD patients. Common use errors in inhaled medications, CAT score, and education background were predictive of and influenced adherence to inhaled medications. It is necessary to strengthen training in Chinese patients about inhaler use and follow-up intensively with patients throughout treatment, especially for patients with risk factors.

Asymmetric Mannich Reaction of Isatin-Derived Ketimines with α-Fluoroindanones Catalyzed by a Chiral Phase-Transfer Catalyst.

A highly enantioselective Mannich reaction of α-fluoroindanones with isatin-derived N-Boc-ketimines catalyzed by a quinine-derived phase-transfer catalyst was developed. A variety of 3-substituted 3-amino-2-oxindoles bearing fluorine-containing, vicinal, tetrasubstituted stereocenters were constructed using this protocol in high yields (83-95%), with moderate to excellent enantioselectivities (66-91%) and high diastereoselectivities (up to >99:1).

Removal of Tetracycline Hydrochloride by Photocatalysis Using Electrospun PAN Nanofibrous Membranes Coated with g-C3N4/Ti3C2/Ag3PO4.

In order to improve the photocatalytic performance of g-C3N4, the g-C3N4/Ti3C2/Ag3PO4 S-type heterojunction catalyst was prepared by electrostatic assembly method, and then the g-C3N4/Ti3C2/Ag3PO4/PAN composite nanofiber membrane was prepared by electrospinning technology. The morphology and chemical properties of the nanofiber membrane were characterized by SEM, FTIR, and XRD, and the photocatalytic degradation of tetracycline hydrochloride (TC) in water by the nanofiber membrane was investigated. The results showed that g-C3N4/Ti3C2/Ag3PO4 could be successfully loaded on PAN and uniformly distributed on the surface of composite nanofiber membrane by electrospinning technology. Increasing the amount of loading and catalyst, lowering the pH value and TC concentration of the system were conducive to the oxidation and degradation of TC. The nano-fiber catalytic membrane had been recycled five times and found to have excellent photocatalytic stability and reusability. The study of catalytic mechanism showed that h+, •OH and •O2- were produced and participated in the oxidation degradation reaction of TC, and •O2- plays a major role in catalysis. Therefore, this work provides a new insight into the construction of high-performance and high-stability photocatalytic system by electrospinning technology.

Rapid, Highly-Efficient and Selective Removal of Anionic and Cationic Dyes from Wastewater Using Hollow Polyelectrolyte Microcapsules.

Herein, poly (allylamine hydrochloride) (PAH)/ poly (styrene sulfonic acid) sodium salt (PSS) microcapsules of (PAH/PSS)2PAH (P2P MCs) and (PAH/PSS)2 (P2 MCs) were obtained by a layer-by-layer method. The P2 MCs show high adsorption capacity for Rhodamine B (642.26 mg/g) and methylene blue (909.25 mg/g), with an extremely low equilibrium adsorption time (~20 min). The P2P MCs exhibited high adsorption capacities of reactive orange K-G (ROKG) and direct yellow 5G (DY5G) which were 404.79 and 451.56 mg/g. Adsorption processes of all dyes onto microcapsules were best described by the Langmuir isotherm model and a pseudo-second-order kinetic model. In addition, the P2P MCs loaded with reactive dyes (P2P-ROKG), could further adsorb rhodamine B (RhB) dye, and P2 MCs that had adsorbed cationic MB dyes could also be used for secondary adsorption treatment of direct dye waste-water, respectively. The present work confirmed that P2P and P2 MCs were expected to become an excellent adsorbent in the water treatment industry.

Reliability and validity test and application of the Chinese version of the Feeling of Satisfaction with Inhaler. / ä¸­æ–‡ç‰ˆå¸å ¥è¯ç‰©æ»¡æ„åº¦é‡è¡¨çš„ä¿¡æ•ˆåº¦æ£€éªŒåŠåº”ç”¨.

OBJECTIVES: Inhaler satisfaction is an important factor affecting inhaler adherence and the efficacy of inhalers in chronic airway diseases. Using a scientific and effective method to assess patients' satisfaction with inhalers is of great significance for improving clinical outcomes. The Feeling of Satisfaction with Inhaler-10 (FSI-10) is specifically designed to assess patients' inhaler satisfaction in chronic airway diseases, but the application research on this scale is not available in China. This study aims to evaluate the reliability and validity of the Chinese version of FSI-10, describe the current status of inhaler satisfaction and discuss the associated variables in Chinese patients with chronic airway disease. METHODS: Based on the English version of FSI-10, items of the Chinese version of FSI-10 were determined after forward⁃backward translation and cultural adaption. Totally, 322 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from the Second Xiangya Hospital of Central South University from June to October 2022. We collected associated clinical variables and inhaler satisfaction using the Chinese version of FSI-10. The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. A multivariate logistic regression was conducted to examine variables related to inhaler satisfaction. RESULTS: The reliability and validity analysis showed that the CVI was 0.983. One factor was extracted from the Chinese version of FSI-10 and the cumulative variance contribution rate was 73.114%. The Cronbach's α of the scale was 0.913, the Guttman's half-reliability coefficient was 0.905, and the test-retest reliability was 0.727 (P<0.001). In addition, the total score of the scale for patients was 38.92±4.26 points and the proportion of high satisfaction (the score of FSI-10≥40) in patients with COPD was significantly lower than that in asthma patients (71.3% vs 87.9%, P<0.01). Older age (age≥70 years) was a risk factor of lower inhaler satisfaction and asthma diagnosis was a protective factor. CONCLUSIONS: The Chinese version of FSI-10 has good reliability and validity in patients with COPD and asthma, which may be further promoted and applied in patients with chronic airway disease in China. Doctors should regularly evaluate the inhaler satisfaction of patients with chronic airway diseases, especially for those elder or with severe symptoms and a long course of illness.

Review on Health Impacts from Domestic Coal Burning: Emphasis on Endemic Fluorosis in Guizhou Province, Southwest China.

Endemic fluorosis in Guizhou Province, Southwest China was firstly reported by Lyth in 1946 and was extensively concerned since the early 1980s. Initially, the pathological cause of endemic fluorosis in Guizhou Province was instinctively ascribed to the drinking water. However, increasing evidences pointed that the major exposure route of fluorine for the local residents is via the roasted foodstuffs, especially the roasted pepper and corn. Source of fluorine in roasted foodstuffs was once blamed on the local coal and subsequently imputed to clay mixed in the coal. In fact, both are probably the source. Geogenic fluorine concentration in soil and clay is indeed high in Guizhou Province, but is not likely to be the direct cause for endemic fluorosis. The real culprit for endemic fluorosis in Guizhou Province is the unhealthy lifestyle of the local residents, who usually roasted their foodstuffs using local coal or briquettes (a mixture of coal and clay), resulting in the elevated fluorine in roasted foodstuffs. Nowadays, endemic fluorosis in Guizhou Province has substantially mitigated. Nevertheless, millions of confirmed cases of dental fluorosis remain left. In addition to endemic fluorosis, other health problems associated with domestic coal burning may also exist, because of the enrichment of toxic/harmful elements in the local coal. It is necessary to determine how serious the situation is and find out the possible solution. As people in other developing countries may suffer from similar health issues, same health issues around the world deserve more attention.

[Roles of CX3CR1 in mediation of post-incision induced mechanical pain hypersensitivity: Effects of acupuncture-combined anesthesia].

Post-incision pain often occurs after surgery and is emergent to be treated in clinic. It hinders the rehabilitation of patients and easily leads to various types of postoperative complications. Acupuncture-combined anesthesia (ACA) is the combination of traditional acupuncture and modern anesthesia, which means acupuncture is applied at acupoints with general anesthesia. It was testified that ACA strengthened the analgesic effect and reduced the occurrence of postoperative pain, but its mechanism was not clear. Numerous reports have shown that chemokine receptor CX3CR1 is involved in the development and progression of many pathological pains. The present study was aimed to reveal whether ACA played the analgesic roles in the post-incision pain by affecting CX3CR1. A model of toe incision pain was established in C57BL/6J mice. The pain threshold was detected by behavioral test, and the expression of CX3CR1 protein was detected by immunohistochemical method and Western blot. The results showed that the significant mechanical allodynia and thermal hyperalgesia were induced by paw incision in the mice. Mechanical allodynia was significantly suppressed by ACA, but thermal hyperalgesia was not changed. CX3CR1 was mainly expressed in microglia in the spinal cord dorsal horn, and its protein level was significantly increased at 3 d after incision compared with that of naïve C57BL/6J mice. ACA did not affect CX3CR1 protein expression at 3 d after incision in the toe incision model mice. Paw withdrawal threshold was significantly increased at 3 d after incision in CX3CR1 knockout (KO) mice compared with that in the C57BL/6J mice. But the analgesic effect of ACA was disappeared in CX3CR1 KO mice. Accordingly, it was also blocked when neutralizing antibody of CX3CR1 was intrathecally injected (i.t.) 1 h before ACA in the C57BL/6J mice. These results suggest that CX3CR1 in microglia is involved in post-incision pain and analgesia of ACA.

Distribution characteristics and source apportionment of polycyclic aromatic hydrocarbons (PAHs) in the Liao River drainage basin, northeast China.

The Liao River drainage basin, which is one of China's seven major rivers basins, is located in northeast China. This region is characterized by important industrial bases including steel factories and oil and chemical plants, all of which have the potential to contribute pollutants to the drainage basin. In this study, 16 polycyclic aromatic hydrocarbons (PAHs) in water and suspended particulate matter (SPM) in the major rivers of the Liao River drainage basin were identified and quantified by gas chromatography mass spectrometry (GC/MS). The total PAH concentrations ranged from 0.4 to 76.5 µg/g (dry weight) in SPM and 32.6 to 108 ng/L in surface water, respectively. Low-ring PAHs (including two- and three-ring PAHs) were dominant in all PAH samples, and the level of low-ring PAHs in surface water was higher than that in SPM. The proportion of two-ring PAHs was the highest, accounting for an average of 68.2 % of the total PAHs in surface water, while the level of three-ring PAHs was the highest in SPM, with an average of 66.3 %. When compared with other river systems, the concentrations of PAHs in the Liao River drainage basin were lower. Identification of the emission sources based on diagnostic ratios suggested petroleum and fossil fuel combustion were important contribution to PAHs in the study area.

SIP30 is required for neuropathic pain-evoked aversion in rats.

SIP30 (SNAP25 interacting protein of 30) is a SNAP25 interaction protein of 30 kDa that functions in neurotransmitter release. Using a chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord and brain and identified sip30, which was upregulated after CCI. Here, we show that CCI induced a bilateral increase of SIP30 in the rostral anterior cingulate cortex (rACC), a key brain region that has been implicated in pain affect. We put rats in a chamber with one half painted white (light area) and the other half painted black (dark area), and measured neuropathic pain-evoked place escape/avoidance paradigm (PEAP) to quantify the level of negative emotion evoked by painful stimuli using a Von Frey hair. Inhibition of CCI-mediated induction of SIP30 by intra-rACC injection of shRNA targeting the rat sip30 gene reduced PEAP. Interestingly, knockdown of SIP30 did not affect CCI-induced evoked pain such as heat hyperalgesia and mechanical allodynia. Neither did it affect general learning and memory. CCI-induced upregulation of SIP30 was correlated with activation of ERK, PKA, and CREB in the rACC. Intra-rACC administration of PKA or ERK inhibitors suppressed CCI-induced SIP30 upregulation and blocked the induction of PEAP. Additionally, knockdown of SIP30 suppressed the frequency of mEPSCs and increased paired-pulse ratios in rACC slices and decreased extracellular glutamate concentrations. Together, our results highlight SIP30 as a target of PKA and ERK in the rACC to mediate neuropathic pain-evoked negative emotion via modulation of glutamate release and excitatory synaptic transmission.

Profile distribution and accumulation characteristics of organic carbon in a karst hillslope based on particle-size fractionation and stable isotope analysis.

Recent studies have highlighted tight coupling between soil aggregate fractions and soil organic carbon (SOC) turnover. However, large uncertainties remain and a mechanistic understanding of geomorphic and land use change effects on carbon storage in soil is still lacking. Taking typical slope of vegetation recovery in karst area as object, the present study analyzed organic carbon content and stable carbon isotope composition (δ13C value) of soil organic matter in bulk and particle size separates of soil on profiles at different topographic positions. The results showed that SOC content decreased gradually in downhill direction. Organic carbon content of sandy soil (50-2000 µm) accounted above 50% in the upper slope positions but in the middle and lower slope soil profiles, organic carbon was mainly stored in silts (2-50 µm) and clays (< 2 µm) which belonged to stable and highly humified SOC. The composition difference of δ13C values in soil profiles reflected the input of plant residues and accumulation characteristics. Organic matter was deposited in different soil particle sizes owing to different degrees of decomposition. Hence, δ13C value can help in identifying the storage and decomposition rates of soil organic matter.

Peripheral TGF-ß1 signaling is a critical event in bone cancer-induced hyperalgesia in rodents.

Pain is the most common symptom of bone cancer. TGF-ß, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-ß1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-ß1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGFßRI and TGFßRII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-ß receptors by the TGFßRI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection of TGF-ß1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not in Trpv1(-/-) mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application of TGF-ß1 significantly potentiated TRPV1 currents and increased [Ca(2+)]i in DRG neurons. Pharmacological studies revealed that the TGF-ß1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-ßR-mediated Smad-independent PKCε and TGF-ß activating kinase 1-p38 pathways. These findings suggest that TGF-ß1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting of TGF-ß1 may ameliorate the bone cancer pain in advanced cancer.

Up-regulation of interleukin-23 induces persistent allodynia via CX3CL1 and interleukin-18 signaling in the rat spinal cord after tetanic sciatic stimulation.

Tetanic stimulation of the sciatic nerve (TSS) induces sciatic nerve injury and long-lasting pain hypersensitivity in rats, and spinal glial activation and proinflammatory cytokines releases are involved. In the present study, we showed that spinal interleukin (IL)-23 and its receptor, IL-23R, are crucial for the development of mechanical allodynia after TSS. In the spinal dorsal horn, both IL-23 and IL-23R are expressed in astrocytes, and this expression is substantially increased after TSS. Inhibition of IL-23 signaling attenuated TSS-induced allodynia and decreased the induction of glial fibrillary acidic protein (GFAP, an astrocytic marker). Conversely, intrathecally delivered IL-23 induced a persistent allodynia. Similar to IL-23 signaling, an increase in IL-18 and its receptor, IL-18R, as well as CX3CL1 and its receptor, CX3CR1, was simultaneously observed in the spinal dorsal horn after TSS. Interestingly, IL-18 and CX3CR1 were exclusively expressed in microglia, while IL-18R was mainly localized in astrocytes. In contrast, CX3CL1 was predominately expressed in neurons and secondarily in astrocytes. The functional inhibition of CX3CL1 and IL-18 signaling attenuated TSS-induced allodynia and suppressed IL-23 and IL-23R upregulation. Activation of CX3CR1 and IL-18R induced similar behavioral and biochemical changes to those observed after TSS. These results indicate that the interaction among CX3CL1, IL-18 and IL-23 signaling in the spinal cord plays a critical role in the development of allodynia. Thus, interrupting this chemokine-cytokine network might provide a novel therapeutic strategy for neuropathic pain.

Estrogen in the anterior cingulate cortex contributes to pain-related aversion.

The rostral anterior cingulate cortex (rACC) is a key structure of pain affect. Whether and how estrogen in the rACC regulates pain-related negative emotion remains unclear. Behaviorally, using formalin-induced conditioned place aversion (F-CPA) in rats, which is believed to reflect the pain-related negative emotion, we found that estrogen receptor (ER) inhibitor ICI 182, 780 (ICI, 7α,17ß-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol) or inhibitor of aromatase androstatrienedione into the rACC completely blocked F-CPA in either sex. An analogous effect was also observed in ovariectomy rats. Furthermore, exogenous estrogen in the absence of a formalin noxious stimulus was sufficient to elicit CPA (E-CPA) in both sexes by activating the membrane estrogen receptors (mERs) and N-methyl-D-aspartic acid (NMDA) receptors (NMDARs). Electrophysiologically, we demonstrated that estrogen acutely enhanced the glutamatergic excitatory postsynaptic currents (EPSCs) in rACC slices by increasing the ratio of NMDA-EPSCs to α-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid -EPSCs and presynaptic glutamate release. Interestingly, a brief exposure to estrogen elicited a persistent enhancement of NMDA-EPSCs, and this NMDA-long-term potentiation required the activation of the mERs, protein kinase A and NMDAR subunit NR2B. Finally, estrogen induced rapid dendritic spine formation in cultured rACC neurons. These results suggest that estrogen in the rACC, as a neuromodulator, drives affective pain via facilitating NMDA receptor-mediated synaptic transmission.

Impact of carbon fiscal policy on Zhejiang Economy-Evidence from E-DSGE.

This paper studies the impact of carbon fiscal policy on the Zhejiang economy through the lens of a DSGE model with an environmental sector. The model was estimated via Bayesian estimation using data from Zhejiang Province for the period from 2005Q1 to 2021Q4. We found that both carbon tax and carbon emission subsidy can improve environmental quality and reduce carbon emissions. However, the subsidy tends to stimulate output and employment more, while both policies have a negative impact on consumption and investment. We suggest that the government should exercise caution in implementing these policies, as their scale of impact is relatively small. The combination of the two policies could neutralize their impact on output but may enhance their impact on other sectors in Zhejiang. However, the structure and timing of these policies matter; implementing a low carbon tax first followed by a high carbon subsidy would be preferable. Furthermore, we examined and concluded that emission technology, particularly at the firm level, can play a significant role in mitigating the negative impact.

Suboptimal peak inspiratory flow rate: a noticeable risk factor for inhaler concordance in patients with chronic airway diseases.

BACKGROUND: Inhaler concordance and the peak inspiratory flow rate (PIFR) are important determinants of treatment effects in patients with chronic airway diseases. Adequate PIFR is required for driving aerosol medication into the lower respiratory tract. However, the relationship between them has not been discussed previously. This study aimed to describe the characteristics of inhaler concordance and PIFR in Chinese patients with chronic airway diseases and discuss the associated variables and the relationship between them. METHODS: In this single-centre, observational study, a total of 680 patients with chronic airway diseases were enrolled from July 2021 to April 2023. We collected data on the socio-demographic and clinical variables of inhaler concordance using the test of adherence to inhalers (TAI) and PIFR. Multivariate logistic regression was conducted to examine variables related to inhaler concordance and PIFR. RESULTS: A total of 49.4% of patients had low concordance. Patients with chronic obstructive pulmonary disease (COPD) were more concordant than patients with asthma (mean TAI score: 43.60 vs 41.20; p<0.01), while there was no difference in concordance between the asthma-COPD overlap group and the asthma or COPD group. Suboptimal PIFR (adjusted OR, 1.61; 95% CI 1.04 to 2.51) increased the risk of poor concordance among all patients, while triple therapy (adjusted OR, 0.60; 95% CI 0.35 to 0.86) reduced the risk. A total of 54.9% of patients had suboptimal PIFR. Older age, lower educational level, use of dry powder inhalers and lower forced expiratory volume in 1 s % predicted were significantly correlated with insufficient PIFR. Subgroup analysis revealed a greater proportion of patients with insufficient PIFR during exacerbation than during the stable phase (61.7% vs 43.5%, p<0.001). CONCLUSION: Inhaler concordance was low, and suboptimal PIFR was a risk factor for poor concordance among Chinese patients with chronic airway diseases. In addition, current inhalation devices may not be suitable, and PIFR reassessment should be considered for patients with COPD during exacerbation. TRIAL REGISTRATION NUMBER: The study was registered in chictr.org.cn (ChiCTR2100052527) on 31 October 2021.

Co-occurrence of elevated arsenic and fluoride concentrations in Wuliangsu Lake: Implications for the genesis of poor-quality groundwater in the (paleo-)Huanghe (Yellow River) catchment, China.

The co-occurrence of high As and F concentrations in saline groundwater in arid and semi-arid regions has attracted considerable attention. However, the factors determining the elevated concentrations of the two elements in surface water in these regions have not been sufficiently studied, and their implications for the poor-quality of local groundwater (high levels of As, F, and salinity) are unknown. A total of 18 water samples were collected from Wuliangsu Lake, irrigation/drainage channels, and the Huanghe (i.e., Yellow River) in the Hetao Basin, China. The pH, concentrations of As and F as well as those of other major elements, and stable isotope (H and O) compositions were analyzed. The water samples had a high pH (7.85-9.01, mean 8.25) and high TDS (402-9778 mg/L, mean 1920 mg/L) values. In six of the 10 lake samples, As concentration was above 10 µg/L (maximum 69.1 µg/L) and, in one of them, F concentration was above 1.5 mg/L. Interestingly, the high As, F, and TDS values simultaneously detected in the lake water were similar to those previously reported in local groundwater, and all water samples showed a significant positive correlation between As and F concentrations (R2 = 0.96, p < 0.01), except for two samples with abnormally high Ca2+ levels. The results of stable isotope analysis and Cl/Br ratios suggested that the lake experienced strong evaporation, which is consistent with the high TDS values. Evaporative concentration is suggested as the main factor contributing to the elevated As and F concentrations in the lake water. In addition, the major ions (e.g., Na+, Cl-, HCO3-, and OH-) and pH in the lake water increased during evaporation, leading to desorption of As and F. Thus, the evaporation process, including evaporative concentration and desorption, was considered primarily responsible for the elevated As and F in the lake water. Based on the results of this study, we presume that the paleolakes in the study area have experienced intense evaporation process. As a result, As, F, and major elements accumulated in sediments (or residual lake water) and were buried in the fluvial basins; then, they were released into the groundwater through multiple (bio)hydrogeochemical processes. By combining the results of this study with those obtained from previous groundwater analyses, we propose a new hypothesis explaining the origin of elevated As and F concentrations in saline groundwater in arid and semi-arid regions.

Development of Fe3O4/DEX/PDA@Au(Raman reporters)@Au-MPBA nanocomposites based multi-hotspot SERS probe for ultrasensitive, reliable, and quantitative detection of glucose in sweat.

Glucose is a key biomarker of diabetes, and effective glucose monitoring methods are crucial to the prevention and management of diabetes. Therefore, in this paper, Fe3O4/DEX/PDA@Au (Raman reporters) @Au nanocomposites were synthetized that with DTNB (5,5'-dithiobis(2-nitrobenzoic)), MMTA (2-mercapto-4-methyl-5-thiazole acetic acid), MBA (4-mercaptobenzoic acid) and 4-Mpy(4-Mercaptopyridine) were used separately as Raman reporters. Fe3O4 and PDA (Polymerized dopamine) could supply more high surface area of active sites and high SERS (Surface-Enhanced Raman Scattering) substrate, which has high stability and reproducibility. Dextran coating is an effective way to prepare biocompatible materials TEM, XRD, TG and VSM were used to analyze the size, morphology and magnetic properties of the nanocomposites. Fe3O4/DEX/PDA@Au(Raman reporters)@Au that integrates a multi-hotspot structure and magnetic separation techniques were studied the enhancement effect of Raman spectra, and glucose solutions with different concentrations were tested. Furthermore, the optimal Fe3O4/DEX/PDA@Au(Raman reporters)@Au nanocomposites were supplied as SERS substrates for detection of glucose accurately and quickly in sweat. SERS signal intensity is linearly correlated with glucose concentration within the measurement range of 5 × 10-3 to 10 mM, and the minimum detectable concentration is 5 µM. The Fe3O4/DEX/PDA@Au(Raman reporters)@Au nanocomposites exhibit high reliability, specificity and repeatability of the strategy were then verified by practical detection of sweat.

ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells.

Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and ß-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Estrogen facilitates spinal cord synaptic transmission via membrane-bound estrogen receptors: implications for pain hypersensitivity.

Recent evidence suggests that estrogen is synthesized in the spinal dorsal horn and plays a role in nociceptive processes. However, the cellular and molecular mechanisms underlying these effects remain unclear. Using electrophysiological, biochemical, and morphological techniques, we here demonstrate that 17ß-estradiol (E2), a major form of estrogen, can directly modulate spinal cord synaptic transmission by 1) enhancing NMDA receptor-mediated synaptic transmission in dorsal horn neurons, 2) increasing glutamate release from primary afferent terminals, 3) increasing dendritic spine density in cultured spinal cord dorsal horn neurons, and 4) potentiating spinal cord long term potentiation (LTP) evoked by high frequency stimulation (HFS) of Lissauer's tract. Notably, E2-BSA, a ligand that acts only on membrane estrogen receptors, can mimic E2-induced facilitation of HFS-LTP, suggesting a nongenomic action of this neurosteroid. Consistently, cell surface biotinylation demonstrated that three types of ERs (ERα, ERß, and GPER1) are localized on the plasma membrane of dorsal horn neurons. Furthermore, the ERα and ERß antagonist ICI 182,780 completely abrogates the E2-induced facilitation of LTP. ERß (but not ERα) activation can recapitulate E2-induced persistent increases in synaptic transmission (NMDA-dependent) and dendritic spine density, indicating a critical role of ERß in spinal synaptic plasticity. E2 also increases the phosphorylation of ERK, PKA, and NR2B, and spinal HFS-LTP is prevented by blockade of PKA, ERK, or NR2B activation. Finally, HFS increases E2 release in spinal cord slices, which can be prevented by aromatase inhibitor androstatrienedione, suggesting activity-dependent local synthesis and release of endogenous E2.