Enhanced autumn phenology model incorporating agricultural drought.

The impacts of various drought types on autumn phenology have yet to be extensively explored. We address the influence of pre-season agricultural and meteorological droughts on autumn phenology in the Northern Hemisphere. To this end, enhanced autumn phenology models incorporating drought factors was developed, contributing to a deeper understanding of these complex interactions. The study reveals that there was no significant trend of advancement or delay in the End of Season (EOS) across the Northern Hemisphere based on SIF estimates from 2001 to 2020. The cumulative and delayed impacts of pre-season agricultural drought on EOS were found to be more pronounced than those associated with meteorological drought. The analysis of various evaluation indexes shows that the performance of the Cooling Degree Days (CDD) model incorporating the Standardized Soil Moisture Drought Index (CDDSSMI) in simulating EOS in the Northern Hemisphere is >14 % higher than that of the standard CDD model. Additionally, the performance of the CDD model with the Standardized Precipitation Index (CDDSPI) in simulating EOS in the Northern Hemisphere is improved by >5.6 % compared to the standard CDD model. A comparison of future EOS projections across various models reveals that the CDD model significantly overestimates EOS in different scenarios (SSP245 and SSP585). The CDDSSMI model projects EOS approximately 7 days earlier than the CDD model, and the CDDSPI model projects EOS approximately 5 days earlier than the CDD model. This study highlights the diverse impacts of drought types on plant autumn phenology and underscores the significance of parameterizing drought impacts in autumn phenology models.

Exploring the causal relationship between glutamine metabolism and leukemia risk: a Mendelian randomization and LC-MS/MS analysis.

Objective: This investigation sought to delineate the causal nexus between plasma glutamine concentrations and leukemia susceptibility utilizing bidirectional Mendelian Randomization (MR) analysis and to elucidate the metabolic ramifications of asparaginase therapy on glutamine dynamics in leukemia patients. Methods: A bidirectional two-sample MR framework was implemented, leveraging genetic variants as instrumental variables from extensive genome-wide association studies (GWAS) tailored to populations of European descent. Glutamine quantification was executed through a rigorously validated Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) protocol. Comparative analyses of glutamine levels were conducted across leukemia patients versus healthy controls, pre- and post-asparaginase administration. Statistical evaluations employed inverse variance weighted (IVW) models, MR-Egger regression, and sensitivity tests addressing pleiotropy and heterogeneity. Results: The MR findings underscored a significant inverse association between glutamine levels and leukemia risk (IVW p = 0.03558833), positing lower glutamine levels as a contributory factor to heightened leukemia susceptibility. Conversely, the analysis disclosed no substantive causal impact of leukemia on glutamine modulation (IVW p = 0.9694758). Notably, post-asparaginase treatment, a marked decrement in plasma glutamine concentrations was observed in patients (p = 0.0068), underlining the profound metabolic influence of the therapeutic regimen. Conclusion: This study corroborates the hypothesized inverse relationship between plasma glutamine levels and leukemia risk, enhancing our understanding of glutamine's role in leukemia pathophysiology. The pronounced reduction in glutamine levels following asparaginase intervention highlights the critical need for meticulous metabolic monitoring to refine therapeutic efficacy and optimize patient management in clinical oncology. These insights pave the way for more tailored and efficacious treatment modalities in the realm of personalized medicine.

Associations between quantitative measures of mammographic density and terminal ductal lobular unit involution in Chinese breast cancer patients.

BACKGROUND: Higher mammographic density (MD), a radiological measure of the proportion of fibroglandular tissue in the breast, and lower terminal duct lobular unit (TDLU) involution, a histological measure of the amount of epithelial tissue in the breast, are independent breast cancer risk factors. Previous studies among predominantly white women have associated reduced TDLU involution with higher MD. METHODS: In this cohort of 611 invasive breast cancer patients (ages 23-91 years [58.4% ≥ 50 years]) from China, where breast cancer incidence rates are lower and the prevalence of dense breasts is higher compared with Western countries, we examined the associations between TDLU involution assessed in tumor-adjacent normal breast tissue and quantitative MD assessed in the contralateral breast obtained from the VolparaDensity software. Associations were estimated using generalized linear models with MD measures as the outcome variables (log-transformed), TDLU measures as explanatory variables (categorized into quartiles or tertiles), and adjusted for age, body mass index, parity, age at menarche and breast cancer subtype. RESULTS: We found that, among all women, percent dense volume (PDV) was positively associated with TDLU count (highest tertile vs. zero: Expbeta = 1.28, 95% confidence interval [CI] 1.08-1.51, ptrend = < .0001), TDLU span (highest vs. lowest tertile: Expbeta = 1.23, 95% CI 1.11-1.37, ptrend = < .0001) and acini count/TDLU (highest vs. lowest tertile: Expbeta = 1.22, 95% CI 1.09-1.37, ptrend = 0.0005), while non-dense volume (NDV) was inversely associated with these measures. Similar trend was observed for absolute dense volume (ADV) after the adjustment of total breast volume, although the associations for ADV were in general weaker than those for PDV. The MD-TDLU associations were generally more pronounced among breast cancer patients ≥ 50 years and those with luminal A tumors compared with patients < 50 years and with luminal B tumors. CONCLUSIONS: Our findings based on quantitative MD and TDLU involution measures among Chinese breast cancer patients are largely consistent with those reported in Western populations and may provide additional insights into the complexity of the relationship, which varies by age, and possibly breast cancer subtype.

Ultrahigh Potassium Storage Capacity of Ca2Si Monolayer with Orderly Multilayered Growth Mechanism.

As the rising renewable energy demands and lithium scarcity, developing high-capacity anode materials to improve the energy density of potassium-based batteries (PBBs) is increasingly crucial. In this work, a unique orderly multilayered growth (OMLG) mechanism on a 2D-Ca2Si monolayer is theoretically demonstrated for potassium storage by first-principles calculations. The global-energy-minimum Ca2Si monolayer is a semiconductor with isotropic mechanical properties and remarkable electrochemical properties, such as a low potassium ion migration energy barrier of 0.07 eV and a low open circuit voltage ranging from 0.224 to 0.003 V. Most notably, 2D-Ca2Si demonstrates an ultrahigh theoretical specific capacity of 5459 mAh g-1 and a total specific capacity of 610 mAh g-1, reaching up to 89% of the capacity of a potassium metal anode. Remarkably, the OMLG mechanism facilitates stable, dendrite-free deposition of hcp-K metal layers on the 2D-Ca2Si surface, where the ultrahigh and gradually converging lattice match as the layers increase is the key to achieving theoretically near-infinite growth. The study theoretically demonstrates the Ca2Si monolayer a highly promising anode material, and offers a novel potassium storage strategy for designing 2D anode materials with high specific capacity, rapid potassium-ion migration, and good safety.

Optical Surface-guided Radiation Therapy for Upper and Lower Limb Sarcomas: An Analysis of Setup Errors and Clinical Target Volume-To-Planning Target Volume Margins.

Purpose: To assess the clinical benefits of surface-guided radiation therapy (SGRT) in terms of setup error, positioning time, and clinical target volume-to-planning target volume (CTV-PTV) margin in extremity soft tissue sarcoma (STS). Methods and Materials: Fifty consecutive patients treated with radiation therapy were selected retrospectively. Treatment setup was performed with either laser-based imaging only (control group), or with laser-based and daily optical surface-based imaging (SGRT group). Pretreatment cone beam computed tomography images were acquired daily for the first 3 to 5 fractions and weekly thereafter, with the frequency adjusted as necessary. Translational and rotational errors were collected. CTV-PTV margin was calculated using the formula, 2.5Σ + 0.7σ. Results: Each group consisted of 10 and 15 upper and lower limb STSs, respectively. For patients with upper limb sarcomas, the translation errors were 1.64 ± 1.34 mm, 1.10 ± 1.50 mm, and 1.24 ± 1.45 mm in the SGRT group, and 1.48 ± 3.16 mm, 2.84 ± 2.85 mm, and 3.14 ± 3.29 mm in control group in the left-right, supero-inferior, and antero-posterior directions, respectively. Correspondingly, for patients with lower limb sarcomas, the translation errors were 1.21 ± 1.65 mm, 1.39 ± 1.71 mm, and 1.48 ± 2.10 mm in the SGRT group, and 1.81 ± 2.60 mm, 2.93 ± 3.28 mm, and 3.53 ± 3.75 mm in control group, respectively. The calculated CTV-PTV margins of the SGRT group and control group were 5.0, 3.8, 4.1 versus 5.9, 9.1, 10.1 mm for upper limb sarcomas; and 4.2, 4.7, 5.2 mm versus 6.3, 9.6, and 11.4 mm for lower limb sarcomas in the left-right, supero-inferior, and antero-posterior directions, respectively. Conclusions: Daily optical surface guidance can effectively improve the setup accuracy of extremity STS patients, and safely reduce the required CTV-PTV margins.

Prediction of Halogenated MXenes as Electrode Materials for Halide-Ion Batteries.

Exploring and developing new rechargeable halide-ion batteries plays an important role in the advancement and growth of the ion battery family. Here, we systematically explored the feasibility of single-layer MXenes and their hydrogenated derivatives as electrode materials for halide-ion batteries via first-principles theory. The calculated results indicate that halide ions (T ions) can be stably and efficiently adsorbed on the surfaces of M2X and M2XH2, with theoretical specific capacities ranging from 227 to 497 mAh g-1. The diffusion barriers of the T ion on MXenes are from 0.55 to 0.10 eV, comparable to those of the Li ion in graphite and LiCoO2. The electronegativity of halide anions displays significant impacts on their discharge voltage plateaus on M2X, with the highest voltage up to 5.60 V for the F ion. As a comparison, the hydrogenation of M2XH2 with less surface activity raises a 2-3 V voltage reduction. All MXene-based full cells of TxTi2C|TyTi2CH2 (where x = 0-2 and y = 2-0) and TxTi2N|TyTi2NH2 (where x = 0-2 and y = 2-0) demonstrated high full battery specific energies for F-, Cl-, and Br-ion batteries, up to 462 Wh kg-1. These results demonstrate the potential of new halide-ion battery designs, paving the way for future research and innovation in battery technology.

Intraventricular Thrombosis and Pulmonary Embolism Post-Nuss Procedure: A Rare Case of Chronic Bar Displacement in a 16-Year-Old Patient.

This novel report presents the first known case, to our knowledge, of a 16-year-old male patient who experienced intraventricular thrombosis and pulmonary embolism after a Nuss procedure for pectus excavatum, attributed to chronic bar displacement. Two years after the operation, the patient experienced post-exercise cough and hemoptysis, which led to his admission. Imaging revealed pulmonary embolism, thrombosis in the right ventricular outflow tract, and lung infiltrative lesions. We hypothesize that the chronic bar displacement led to its embedment in the right ventricle, resulting in thrombus formation, which subsequently contributed to partial pulmonary embolism. Surgery revealed the bars' intrusion into the right ventricle and lung. This case highlights the risk of severe complications from bar displacement in the Nuss procedure, which necessitates long-term follow-up evaluation, caution against strenuous activities after surgery, and use of thoracoscopic guidance during bar implantation and removal. It underscores the importance of vigilant evaluation for late-stage complications in patients with respiratory distress or thrombosis after a Nuss procedure.

In Vivo Cavitation-based Aberration Correction of Histotripsy in Porcine Liver.

Histotripsy is a non-invasive ablation technique that focuses ultrasound pulses into the body to destroy tissues via cavitation. Heterogeneous acoustic paths through tissue introduce phase errors that distort and weaken the focus, requiring additional power output from the histotripsy transducer to perform therapy. This effect, termed phase aberration, limits the safety and efficacy of histotripsy ablation. It has been shown in vitro that the phase errors from aberration can be corrected by receiving the acoustic signals emitted by cavitation. For transabdominal histotripsy in vivo, however, cavitation-based aberration correction is complicated by acoustic signal clutter and respiratory motion. This study develops a method that enables robust, effective cavitation-based aberration correction in vivo and evaluates its efficacy in the swine liver. The method begins with a high-speed pulsing procedure to minimize the effects of respiratory motion. Then, an optimal phase correction is obtained in the presence of acoustic clutter by filtering with the singular value decomposition. This aberration correction method reduced the power required to generate cavitation in the liver by 26% on average (range: 0% to 52%) and required ~2 s for signal acquisition and processing per focus location. These results suggest that the cavitation-based method could enable fast and effective aberration correction for transabdominal histotripsy.

Enzyme-linked immunoassay for simultaneous detection of methyl parathion and sibutramine in apple cider vinegar.

Methyl parathion, a highly toxic, efficient, and persistent organophosphorus pesticide, is widely used in China. Sibutramine, a non-amphetamine central nervous system depressant, helps lose weight by disrupting hormone regulation, stimulating sympathetic nerves, and suppressing appetite. However, some unethical businesses fail to properly handle raw materials in foods like apple cider vinegar, leading to residual methyl parathion in apples or illegal excessive addition of sibutramine. Therefore, it is imperative to develop an immunoassay for the rapid detection of methyl parathion and sibutramine. The corresponding two haptens were prepared and coupled with the carrier proteins according to methyl parathion-sulfur-bovine serum protein (BSA)/chicken ovalbumin (OVA)-sibutramine (20 : 1 : excess, 15 : 1 : excess, 10 : 1 : excess, and 5 : 1 : excess), and sibutramine-BSA/OVA-methyl parathion (20 : 1 : excess, 10 : 1 : excess: 5 : 1 : excess, and 0 : 1 : excess). The result shows that the inhibition rate of the antibody obtained by methyl parathion-BSA/OVA-sibutramine (20 : 1 : excess) was higher than that of sibutramine-BSA/OVA-methyl parathion, which was 67.93%, and the concentration of methyl parathion was 8.65 ng mL-1 at this inhibition rate. Thus, methyl parathion-BSA/OVA-sibutramine (8.65 : 1 : excess) and the corresponding antibodies were selected for subsequent method establishment. By changing the concentration of the coating and antibody, the inhibition rate was found when the coating was 0.125 ng mL-1 and the antibody was diluted 4000 times. The antibody was used to develop a standard curve for the detection of sibutramine at the half-maximum inhibitory concentration (IC50) is 4.59 ng mL-1, the limit of detection (IC10) is 2.21 ng mL-1, the detection range is 2.89 to 7.28 ng mL-1, methyl p-phosphorus at the half-maximum inhibitory concentration (IC50) is 15.34 ng mL-1, the limit of detection (IC10) is 0.42 ng mL-1, the detection range is ng mL-1. Under these conditions, the recovery rate was between 88% and 102%, within reasonable limits, indicating the successful establishment of a rapid enzyme-linked ELISA assay.

Structure of cryptophyte photosystem II-light-harvesting antennae supercomplex.

Cryptophytes are ancestral photosynthetic organisms evolved from red algae through secondary endosymbiosis. They have developed alloxanthin-chlorophyll a/c2-binding proteins (ACPs) as light-harvesting complexes (LHCs). The distinctive properties of cryptophytes contribute to efficient oxygenic photosynthesis and underscore the evolutionary relationships of red-lineage plastids. Here we present the cryo-electron microscopy structure of the Photosystem II (PSII)-ACPII supercomplex from the cryptophyte Chroomonas placoidea. The structure includes a PSII dimer and twelve ACPII monomers forming four linear trimers. These trimers structurally resemble red algae LHCs and cryptophyte ACPI trimers that associate with Photosystem I (PSI), suggesting their close evolutionary links. We also determine a Chl a-binding subunit, Psb-γ, essential for stabilizing PSII-ACPII association. Furthermore, computational calculation provides insights into the excitation energy transfer pathways. Our study lays a solid structural foundation for understanding the light-energy capture and transfer in cryptophyte PSII-ACPII, evolutionary variations in PSII-LHCII, and the origin of red-lineage LHCIIs.

Interlayer Delocalized Electrons Activate Basal Plane for Ultrahigh-Current-Density Hydrogen Evolution.

The basal plane of transition metal dichalcogenides (TMDCs) is inert for the hydrogen evolution reaction (HER) due to its low-efficiency charge transfer kinetics. We propose a strategy of filling the van der Waals (vdW) layer with delocalized electrons to enable vertical penetration of electrons from the collector to the adsorption intermediate vertically. Guided by density functional theory, we achieve this concept by incorporating Cu atoms into the interlayers of tantalum disulfide (TaS2). The delocalized electrons of d-orbitals of the interlayered Cu can constitute the charge transfer pathways in the vertical direction, thus overcoming the hopping migration through vdW gaps. The vertical conductivity of TaS2 increased by 2 orders of magnitude. The TaS2 basal plane HER activity was extracted with an on-chip microcell. Modified by the delocalized electrons, the current density increased by 20 times, reaching an ultrahigh value of 800 mA cm-2 at -0.4 V without iR compensation.

Neuronavigation-Guided Transcranial Histotripsy (NaviTH) System.

OBJECTIVE: The goal of the work described here was to develop the first neuronavigation-guided transcranial histotripsy (NaviTH) system and associated workflow for transcranial ablation. METHODS: The NaviTH system consists of a 360-element, 700 kHz transmitter-receiver-capable transcranial histotripsy array, a clinical neuronavigation system and associated equipment for patient-to-array co-registration and therapy planning and targeting software systems. A workflow for NaviTH treatments, including pre-treatment aberration correction, was developed. Targeting errors stemming from target registration errors (TREs) during the patient-to-array co-registration process, as well as focal shifts caused by skull-induced aberrations, were investigated and characterized. The NaviTH system was used in treatments of two <96 h post-mortem human cadavers and in experiments in two excised human skullcaps. RESULTS: The NaviTH was successfully used to create ablations in the cadaver brains as confirmed in post-treatment magnetic resonance imaging A total of three ablations were created in the cadaver brains, and targeting errors of 9, 3.4 and 4.4 mm were observed in corpus callosum, septum and thalamus targets, respectively. Errors were found to be caused primarily by TREs resulting from transducer tracking instrument design flaws and imperfections in the treatment workflow. Transducer tracking instrument design and workflow improvements reduced TREs to <2 mm, and skull-induced focal shifts, following pre-treatment aberration correction, were 0.3 mm. Total targeting errors of the NaviTH system following the noted improvements were 2.5 mm. CONCLUSIONS: The feasibility of using the first NaviTH system in a human cadaver model has been determined. Although accuracy still needs to be improved, the proposed system has the potential to allow for transcranial histotripsy therapies without requiring active magnetic resonance treatment guidance.

Calcium signaling crosstalk between the endoplasmic reticulum and mitochondria, a new drug development strategies of kidney diseases.

Calcium (Ca2+) acts as a second messenger and constitutes a complex and large information exchange system between the endoplasmic reticulum (ER) and mitochondria; this process is involved in various life activities, such as energy metabolism, cell proliferation and apoptosis. Increasing evidence has suggested that alterations in Ca2+ crosstalk between the ER and mitochondria, including alterations in ER and mitochondrial Ca2+ channels and related Ca2+ regulatory proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP3R), and calnexin (CNX), are closely associated with the development of kidney disease. Therapies targeting intracellular Ca2+ signaling have emerged as an emerging field in the treatment of renal diseases. In this review, we focused on recent advances in Ca2+ signaling, ER and mitochondrial Ca2+ monitoring methods and Ca2+ homeostasis in the development of renal diseases and sought to identify new targets and insights for the treatment of renal diseases by targeting Ca2+ channels or related Ca2+ regulatory proteins.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Establishment of enzyme-linked immunosorbent assay for aristolochic acid.

In recent years, the nephrotoxicity and carcinogenicity of aristolochic acid have attracted worldwide attention, and the traditional Chinese medicine containing this ingredient has been banned in many places, affecting the TCM industry. To meet this challenge, researchers have developed various detection methods, such as high-performance liquid chromatography, gas chromatography-mass spectrometry and thin-layer chromatography. A rapid detection method must therefore be developed to ensure safety. A polyclonal antibody capable of recognizing aristolochic acid was prepared, and an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established to detect the amount of aristolochic acid in the sample to be measured. Methods Using 1-(4-chlorophenyl) cyclobutylamine as a hapten, immunogens and coating antigens were obtained by coupling with bovine serum albumin (BSA) and chicken ovalbumin (OVA) using the active ester method. UV scanning confirmed the successful coupling of the conjugate, and New Zealand white rabbits were immunized. The obtained antibody serum was screened for the best antibody by ic-ELISA detection. Use the chessboard method to determine three optimal combinations of original coating concentration and antibody dilution ratio, establish a standard curve for each combination to obtain the best combination, and establish a rapid detection method. Finally, the standard aristolochic acid A was added to the purchased apple vinegar and canned coffee for recycling experiments to verify the detection method.By changing the antigen antibody concentration, the antibody showed the highest sensitivity to aristolochic acid standard at the original coating, 1000-fold dilution, IC50 of 24.88 ng/mL, limit of detection IC10 of 3.19 ng/mL, and detection range IC20-IC80 of 6.81-90.91 ng/mL. The recovery experiments under this conditions yielded a recovery rate of 92%-105%, within reasonable limits, indicating the success of the ELISA rapid detection method. Conclusion The enzyme-linked immunoassay method established in this paper can quickly detect the content of aristolochic acid in the sample to be tested, and the antibody prepared by this method has good broad-spectrum and can detect other aristolochic acid, such as aristolochic acid A, aristolochic acid B, aristolochic acid C, and aristolochic acid D.

Calcium-sensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats.

Chronic inflammation is a key element in the progression of essential hypertension (EH). Calcium plays a key role in inflammation, so its receptor, the calcium-sensing receptor (CaSR), is an essential mediator of the inflammatory process. Compelling evidence suggests that CaSR mediates inflammation in tissues and immune cells, where it mediates their activity and chemotaxis. Macrophages (Mφs) play a major role in the inflammatory response process. This study provided convincing evidence that R568, a positive regulator of CaSR, was effective in lowering blood pressure in spontaneously hypertensive rats (SHRs), improving cardiac function by alleviating cardiac hypertrophy and fibrosis. R568 can increase the content of CaSR and M2 macrophages (M2Mφs, exert an anti-inflammatory effect) in myocardial tissue, reduce M1 macrophages (M1Mφs), which have a pro-inflammatory effect in this process. In contrast, NPS2143, a negative state regulator of CaSR, exerted the opposite effect in all of the above experiments. Following this study, R568 increased CaSR content in SHR myocardial tissue, lowered blood pressure, promoted macrophages to M2Mφs and improved myocardial fibrosis, but interestingly, both M1Mφs and M2Mφs were increased in the peritoneal cavity of SHRs, the number of M2Mφs remained lower than M1Mφs. In vitro, R568 increased CaSR content in RAW264.7 cells (a macrophage cell line), regulating intracellular Ca2+ ([Ca2+]i) inhibited NOD-like receptor family protein 3 (NLRP3) inflammasome activation and ultimately prevented its conversion to M1Mφs. The results showed that a decrease in CaSR in hypertensive rats causes further development of hypertension and cardiac damage. EH myocardial remodeling can be improved by CaSR overexpression by suppressing NLRP3 inflammasome activation and macrophage polarization toward M1Mφs and increasing M2Mφs.

Conjugated Polymer/Recombinant Escherichia coli Biohybrid Systems for Photobiocatalytic Hydrogen Production.

Biohybrid photocatalysts are composite materials that combine the efficient light-absorbing properties of synthetic materials with the highly evolved metabolic pathways and self-repair mechanisms of biological systems. Here, we show the potential of conjugated polymers as photosensitizers in biohybrid systems by combining a series of polymer nanoparticles with engineered Escherichia coli cells. Under simulated solar light irradiation, the biohybrid system consisting of fluorene/dibenzo [b,d]thiophene sulfone copolymer (LP41) and recombinant E. coli (i.e., a LP41/HydA BL21 biohybrid) shows a sacrificial hydrogen evolution rate of 3.442 mmol g-1 h-1 (normalized to polymer amount). It is over 30 times higher than the polymer photocatalyst alone (0.105 mmol g-1 h-1), while no detectable hydrogen was generated from the E. coli cells alone, demonstrating the strong synergy between the polymer nanoparticles and bacterial cells. The differences in the physical interactions between synthetic materials and microorganisms, as well as redox energy level alignment, elucidate the trends in photochemical activity. Our results suggest that organic semiconductors may offer advantages, such as solution processability, low toxicity, and more tunable surface interactions with the biological components over inorganic materials.

Engineering Efferocytosis-Mimicking Nanovesicles to Regulate Joint Anti-Inflammation and Peripheral Immunosuppression for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis-mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including "find me" and "eat me" signals for professional (macrophage) or non-professional phagocytes (T lymphocyte), and "apoptotic metabolite" for metabolite digestion. We showed that efferocytosis-mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen-induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis-mimicking nanovesicles effectively maintained the pro-inflammatory M1/anti-inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis-mimicking nanovesicles for RA immunotherapy.

Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200 mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400 mg (n = 12); group 3-single dose study with pivmecillinam 600 mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on Cmax and AUC0-t of pivmecillinam and Cmax of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24 h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600 mg) or multiple-dose (400 mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.

The Relationship Between Psychological Conditions and Gastrointestinal Symptoms of Medical Students During the COVID-19 Pandemic.

Objective: This study aims to explore the nexus between students' psychological well-being and the manifestation of gastrointestinal symptoms (GISs) amid the health lockdown enforced in Xi'an, focusing on the student populace of Xi'an Medical College and Shaanxi University of Traditional Chinese Medicine. Materials and methods: A survey encompassing psychological parameters and GISs was administered to a randomized cohort of 1327 college students drawn from Xi'an Medical College and Shaanxi University of Traditional Chinese Medicine. The survey instrument was developed utilizing the Questionnaire Star platform. Subsequent to data collection, analysis was performed using GraphPad Prism 9 and SPSS 22.0. Results: Comparative analysis revealed statistically significant disparities (P < 0.05) in various GISs between the periods during and preceding the health lockdown, encompassing symptoms such as nausea/vomiting, acid reflux, postprandial fullness/early satiety, anorexia, decreased appetite, bloating, abdominal discomfort, abdominal pain, diarrhea, and constipation. Notably, the mean score for Generalized Anxiety Disorder 7 (GAD-7) was 3.31±3.92, indicating mild anxiety, while the mean score for Patient Health Questionnaire-2 (PHQ-2) was 1.15±1.28, suggesting mild depression. Detailed evaluation of anxiety revealed prevalence rates of 34% among respondents, with 34.2% of these individuals reporting concurrent GISs, while among those evaluated for depression (38.8% of the sample), 44.2% reported concurrent GISs. Furthermore, multiple linear regression analysis unveiled a negative correlation between GISs during the health lockdown and lifestyle scores, while positive correlations were observed with GISs preceding the lockdown, anxiety, and depression. The formulated multiple linear regression equation for GISs during the health lockdown is delineated as follows: 14.693-0.342 life style + 0.725GISs before health lockdown + 0.218anxiety + 0.564 depression. Conclusion: This investigation underscores the substantial impact of anxiety and depression on the student body, accentuating their role in precipitating GISs during health lockdown situations. The psychological well-being of medical students during exigent circumstances such as natural disasters warrants heightened attention, necessitating proactive measures aimed at emotional regulation to mitigate the onset of GISs.