The evolutionary features and roles of single nucleotide variants and charged amino acid mutations in influenza outbreaks during NPI period.

The epidemic and outbreaks of influenza B Victoria lineage (Bv) during 2019-2022 led to an analysis of genetic, epitopes, charged amino acids and Bv outbreaks. Based on the National Influenza Surveillance Network (NISN), the Bv 72 strains isolated during 2019-2022 were selected by spatio-temporal sampling, then were sequenced. Using the Compare Means, Correlate and Cluster, the outbreak data were analyzed, including the single nucleotide variant (SNV), amino acid (AA), epitope, evolutionary rate (ER), Shannon entropy value (SV), charged amino acid and outbreak. With the emergence of COVID-19, the non-pharmaceutical interventions (NPIs) made Less distant transmission and only Bv outbreak. The 2021-2022 strains in the HA genes were located in the same subset, but were distinct from the 2019-2020 strains (P < 0.001). The codon G → A transition in nucleotide was in the highest ratio but the transversion of C → A and T → A made the most significant contribution to the outbreaks, while the increase in amino acid mutations characterized by polar, acidic and basic signatures played a key role in the Bv epidemic in 2021-2022. Both ER and SV were positively correlated in HA genes (R = 0.690) and NA genes (R = 0.711), respectively, however, the number of mutations in the HA genes was 1.59 times higher than that of the NA gene (2.15/1.36) from the beginning of 2020 to 2022. The positively selective sites 174, 199, 214 and 563 in HA genes and the sites 73 and 384 in NA genes were evolutionarily selected in the 2021-2022 influenza outbreaks. Overall, the prevalent factors related to 2021-2022 influenza outbreaks included epidemic timing, Tv, Ts, Tv/Ts, P137 (B → P), P148 (B → P), P199 (P → A), P212 (P → A), P214 (H → P) and P563 (B → P). The preference of amino acid mutations for charge/pH could influence the epidemic/outbreak trends of infectious diseases. Here was a good model of the evolution of infectious disease pathogens. This study, on account of further exploration of virology, genetics, bioinformatics and outbreak information, might facilitate further understanding of their deep interaction mechanisms in the spread of infectious diseases.

Patient-specific finite element analysis of four different fixation methods for transversely unstable radial head fractures.

Plate fixation is a common treatment option for radial head fractures (RHFs). Due to the benefits of less invasiveness and fewer complications of internal fixation, the application of small-diameter headless compression screws (HCSs) to treat RHFs has become a new trend. This study aimed to compare the mechanical stability of four distinct internal fixation protocols for transversely unstable RHFs via finite element analysis. Using computed tomography data from 10 patients, we developed 40 patient-specific FE models of transversely unstable RHFs fixed by parallel, crossed, and tripod HCSs and mini-T plate (MTP). Under simulated physiological loading of the elbow joint, the construct stiffness, displacement, and von Mises stresses were evaluated and verified by a biomechanical experiment. Under shear loading, the MTP group exhibited lower construct stiffness, larger displacement, and higher Von Mises stress than the HCSs group. The stiffness of tripod HCSs was greater than parallel and crossed screw fixation techniques. There was a strong relationship between apparent bone density and construct stiffness (R = 0.98 to 0.99). In the treatment of transversely unstable RHFs, HCSs have superior biomechanical stability than MTP. The tripod technique was also more stable than parallel and crossed fixation.

Nitrogen-doped titanium dioxide/schwertmannite nanocomposites as heterogeneous photo-Fenton catalysts with enhanced efficiency for the degradation of bisphenol A.

Potential health risks related to environmental endocrine disruptors (EEDs) have aroused research hotspots at the forefront of water treatment technologies. Herein, nitrogen-doped titanium dioxide/schwertmannite nanocomposites (N-TiO2/SCH) have been successfully developed as heterogeneous catalysts for the degradation of typical EEDs via photo-Fenton processes. Due to the sustainable Fe(III)/Fe(II) conversion induced by photoelectrons, as-prepared N-TiO2/SCH nanocomposites exhibit much enhanced efficiency for the degradation of bisphenol A (BPA; ca. 100% within 60 min under visible irradiation) in a wide pH range of 3.0-7.8, which is significantly higher than that of the pristine schwertmannite (ca. 74.5%) or N-TiO2 (ca. 10.8%). In this photo-Fenton system, the efficient degradation of BPA is mainly attributed to the oxidation by hydroxyl radical (•OH) and singlet oxygen (1O2). Moreover, the possible catalytic mechanisms and reaction pathway of BPA degradation are systematically investigated based on analytical and photoelectrochemical analyses. This work not only provides a feasible means for the development of novel heterogeneous photo-Fenton catalysts, but also lays a theoretical foundation for the potential application of mineral-based materials in wastewater treatment.

Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects.

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Ti-Doped AgNbO3 as Novel Dense Diffusion Barriers of Limiting Current Oxygen Sensors.

The oxygen sensors with limiting current derived from a dense diffusion barrier have an excellent advantage of detecting oxygen partial pressure by controlling the ratio of air and fuel in combustion environments. Therefore, AgNb1-xTixO3-δ (wherein x varies from 0.1 to 0.3) was prepared as such a dense diffusion barrier layer for sensor application. Among the investigated compositions as a new condensed barrier for the diffusion of sensors, AgNb1-xTixO3-δ (x = 0.1, 0.2, 0.3) exhibits oxygen ionic conductivities from 1.37 × 10-4 to 5.78 × 10-3 S·cm-1 in the temperature range of 600-900 °C and outstanding stable electrochemical properties. Herein, we employ these novel materials as dense diffusion barriers and 8 mol % zirconia stabilized by yttria (8YSZ) as a solid-state electrolyte for the fabrication of the oxygen sensors with limiting current. We observed a direct connection between the limiting current and oxygen content within the interval of 0.5-5.0 mol % at 800 °C and a low working voltage. The increase of Ti-doping amount in AgNbO3 accelerates the sensing response to oxygen gas and promotes the service life of the sensor.

[Identification of Complex and Combined Antibody Consisted of Anti-c, Anti-E, Anti-Jka and Anti-Fya].

OBJECTIVE: To investigate the role of multiple serological methods in the identification of complex antibodies. METHODS: The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. RESULTS: The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jka antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies. CONCLUSION: It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies exist in the patient's serum by multiple serological methods.

Femoral neck system and cannulated compression screws in the treatment of non-anatomical reduction Pauwels type-III femoral neck fractures: A finite element analysis.

BACKGROUND: High shear force is a major factor detrimental to the healing of vertical femoral neck fractures. In addition to firm fixation, reduction quality is crucial for postoperative stability. The present study aimed to compare the biomechanical stability of the newly invented femoral neck system and three inverted-triangle cannulated compression screws treatments for non-anatomical reduction of Pauwels type-III femoral neck fractures. METHODS: A total of 18 non-anatomical reduction Pauwels type-III femoral neck fracture finite element models were fabricated and fixed using three inverted-triangle cannulated compression screws or the femoral neck system. A 1950-N force was applied to the femoral head to simulate the physiological load during a single-leg stance. Parameters of the maximum total deformation, the interfragmentary gap, and the maximum von Mises stress of the implants and the proximal femur were analyzed. FINDINGS: The results of the maximum total deformation, interfragmentary gap, and maximum von Mises stress of the implants in the negative-negative buttress model fixed by the femoral neck system were the largest among all groups (3.58 mm, 0.252 mm, and 729.68 MPa, respectively). In contrast, the anatomical-anatomical reduction model fixed by three inverted-triangle cannulated compression screws demonstrated the minimum total deformation, interfragmentary gap, and minimum von Mises stress of implants (1.107 mm, 0.09 mm, and 189.83 MPa, respectively). INTERPRETATION: Anatomical reduction or positive buttress in femoral neck fractures should be recommended during fracture reduction. The femoral neck system showed weaker biomechanical stability than three inverted-triangle cannulated compression screws in treating Pauwels type-III femoral neck fractures.

Mechanism insights into photo-assisted peroxymonosulfate activation on oxygen vacancy-enriched nolanites via an electron transfer regime.

The utilization of photo-assisted persulfate activation for the removal of organic contaminants in water has garnered significant research interest in recent times. However, there remains a lack of clarity regarding specific contributions of light irradiation and catalyst structure in this process. Herein, a photo-assisted peroxymonosulfate (PMS) activation system is designed for the highly efficient degradation of organic contaminants on oxygen vacancy-enriched nolanites (Vo-FVO). Results suggest that the degradation of bisphenol A (BPA) in this system is a nonradical-dominated process via an electron transfer regime, in which VO improves the local electron density and thus facilitates the electron shuttling between BPA and PMS. During BPA degradation, PMS adsorbed at the surface of FVO-180 withdraws electrons near VO and forms FVO-PMS* complexes. Upon light irradiation, photoelectrons effectively restore the electron density around VO, thereby enabling a sustainable electron transfer for the highly efficient degradation of BPA. Overall, this work provides new insights into the mechanism of persulfate activation based on defects engineering in nolanite minerals.

Application of a time-delay SIR model with vaccination in COVID-19 prediction and its optimal control strategy.

In the classical infectious disease compartment model, the parameters are fixed. In reality, the probability of virus transmission in the process of disease transmission depends on the concentration of virus in the environment, and the concentration depends on the proportion of patients in the environment. Therefore, the probability of virus transmission changes with time. Then how to fit the parameters and get the trend of the parameters changing with time is the key to predict the disease course with the model. In this paper, based on the US COVID-19 epidemic statistics during calibration period, the parameters such as infection rate and recovery rate are fitted by using the linear regression algorithm of machine science, and the laws of these parameters changing with time are obtained. Then a SIR model with time delay and vaccination is proposed, and the optimal control strategy of epidemic situation is analyzed by using the optimal control theory and Pontryagin maximum principle, which proves the effectiveness of the control strategy in restraining the transmission of COVID-19. The numerical simulation results show that the time-varying law of the number of active cases obtained by our model basically conforms to the real changing law of the US COVID-19 epidemic statistics during calibration period. In addition, we have predicted the changes in the number of active cases in the COVID-19 epidemic in the USA over time in the future beyond the calibration cycle, and the predicted results are more in line with the actual epidemic data.

Conductivity and aging behavior of Sr(Ti0.6Fe0.4)1-x O3-δ mixed conductor materials.

Perovskite materials play a significant role in oxygen sensors due to their fascinating electrical and ionic conductivities. The sol-gel technique was employed to prepare various compositions of B-site-deficient Fe-doped SrTiO3 (iron-doped strontium titanate) or Sr(Ti0.6Fe0.4)1-x O3-δ , where x = 0.01, 0.02, and 0.03. The XRD results revealed that the principle crystalline phase of the samples was the cubic perovskite structure. The B-site deficiency improved the ionic and total conductivities of Sr(Ti0.6Fe0.4)1-x O3-δ . A small polaron conduction behavior occurred in the total electrical conductivity. The XPS results showed that the oxygen vacancy value decreased with the rise in the amount of B-site deficiencies. A lower B-site deficiency amount could produce more oxygen vacancies in the lattice but resulted in the ordering of vacancies and then lower ionic conductivity. The aging behavior was caused by the ordering of oxygen vacancies and resulted in a degeneration of electrical features under a long service time. Conversely, augmentation of the B-site deficiency amount inhibited the tendency for the ordering of oxygen vacancies and then promoted the electrical performance under a long usage time. The conduction mechanism of oxygen ions through oxygen vacancies was thoroughly investigated and discussed. The current study presents a feasible approach to ameliorate the physical features of conductors through doping the B-site of the perovskite layer with Fe, which would be a fruitful approach for numerous applications, including oxygen sensors and fuel cells anodes.

Single-molecule analysis of DNA-binding proteins from nuclear extracts (SMADNE).

Single-molecule characterization of protein-DNA dynamics provides unprecedented mechanistic details about numerous nuclear processes. Here, we describe a new method that rapidly generates single-molecule information with fluorescently tagged proteins isolated from nuclear extracts of human cells. We demonstrated the wide applicability of this novel technique on undamaged DNA and three forms of DNA damage using seven native DNA repair proteins and two structural variants, including: poly(ADP-ribose) polymerase (PARP1), heterodimeric ultraviolet-damaged DNA-binding protein (UV-DDB), and 8-oxoguanine glycosylase 1 (OGG1). We found that PARP1 binding to DNA nicks is altered by tension, and that UV-DDB did not act as an obligate heterodimer of DDB1 and DDB2 on UV-irradiated DNA. UV-DDB bound to UV photoproducts with an average lifetime of 39 seconds (corrected for photobleaching, τc), whereas binding lifetimes to 8-oxoG adducts were < 1 second. Catalytically inactive OGG1 variant K249Q bound oxidative damage 23-fold longer than WT OGG1, at 47 and 2.0 s, respectively. By measuring three fluorescent colors simultaneously, we also characterized the assembly and disassembly kinetics of UV-DDB and OGG1 complexes on DNA. Hence, the SMADNE technique represents a novel, scalable, and universal method to obtain single-molecule mechanistic insights into key protein-DNA interactions in an environment containing physiologically-relevant nuclear proteins.

Nsun2 coupling with RoRγt shapes the fate of Th17 cells and promotes colitis.

T helper 17 (Th17) cells are a subset of CD4+ T helper cells involved in the inflammatory response in autoimmunity. Th17 cells secrete Th17 specific cytokines, such as IL-17A and IL17-F, which are governed by the master transcription factor RoRγt. However, the epigenetic mechanism regulating Th17 cell function is still not fully understood. Here, we reveal that deletion of RNA 5-methylcytosine (m5C) methyltransferase Nsun2 in mouse CD4+ T cells specifically inhibits Th17 cell differentiation and alleviates Th17 cell-induced colitis pathogenesis. Mechanistically, RoRγt can recruit Nsun2 to chromatin regions of their targets, including Il17a and Il17f, leading to the transcription-coupled m5C formation and consequently enhanced mRNA stability. Our study demonstrates a m5C mediated cell intrinsic function in Th17 cells and suggests Nsun2 as a potential therapeutic target for autoimmune disease.

PGAM4 silencing inhibited glycolysis and chemoresistance to temozolomide in glioma cells.

Gliomas account for about 80% of malignant brain tumors. The incidence of a new brain tumor is 6.4 per 100,000 persons per year with an overall 5-year survival rate of 33.4%. Regardless of the great advances that have been made in recent years, the causes and pathogenesis of glioma remain unclear. Here we study how phosphoglycerate mutase 4 (PGAM4) contributes to glioma. Using a variety of methods to examine glioma cell viability, proliferation, apoptosis, glycolysis, as well as ChIP coanalysis with modified histone H3, we showed that PGAM4 was significantly upregulated in patients with glioma and associated with poor survival. Silencing PGAM4 attenuated cell viability, proliferation, and glycolysis in T98G cells and suppressed tumor growth in vivo, while overexpressing PGAM4 promoted cell viability, proliferation, and glycolysis in U251 cells via regulating glycolysis pathway. Study also revealed that PGAM4 was regulated by EP300-mediated modifications of H3K27ac. PGAM4 silencing inhibited cell viability and proliferation, suppressed tumor growth, and decreased chemoresistance to temozolomide in glioma cells through suppressing glycolysis.

Cooperative interaction between AAG and UV-DDB in the removal of modified bases.

UV-DDB is a DNA damage recognition protein recently discovered to participate in the removal of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxoG) by stimulating multiple steps of base excision repair (BER). In this study, we examined whether UV-DDB has a wider role in BER besides oxidized bases and found it has specificity for two known DNA substrates of alkyladenine glycosylase (AAG)/N-methylpurine DNA glycosylase (MPG): 1, N6-ethenoadenine (ϵA) and hypoxanthine. Gel mobility shift assays show that UV-DDB recognizes these two lesions 4-5 times better than non-damaged DNA. Biochemical studies indicated that UV-DDB stimulated AAG activity on both substrates by 4- to 5-fold. Native gels indicated UV-DDB forms a transient complex with AAG to help facilitate release of AAG from the abasic site product. Single molecule experiments confirmed the interaction and showed that UV-DDB can act to displace AAG from abasic sites. Cells when treated with methyl methanesulfonate resulted in foci containing AAG and UV-DDB that developed over the course of several hours after treatment. While colocalization did not reach 100%, foci containing AAG and UV-DDB reached a maximum at three hours post treatment. Together these data indicate that UV-DDB plays an important role in facilitating the repair of AAG substrates.

Targeted therapy of atherosclerosis by pH-sensitive hyaluronic acid nanoparticles co-delivering all-trans retinal and rapamycin.

Atherosclerosis, the leading cause of death in the elderly worldwide, is typically characterized by elevated reactive oxygen species (ROS) levels and a chronic inflammatory state at the arterial plaques. Herein, pH-sensitive nanoparticles (HRRAP NPs) co-delivering all-trans retinal (ATR), an antioxidant linked to hyaluronic acid (HA) through a pH-sensitive hydrazone bond, and rapamycin (RAP), an anti-atherosclerotic drug loaded into the nanoparticle core, are developed for targeted combination therapy of atherosclerosis. In this way, HRRAP NPs might simultaneously reduce ROS levels via ATR antioxidant activity and reduce inflammation via the anti-inflammatory effect of RAP. In response to mildly acidic conditions mimicking the lesional inflammation in vitro, HRRAP NPs dissociated and both ATR and RAP were effectively released. The developed HRRAP NPs effectively inhibited pro-inflammatory macrophage proliferation, and displayed dose- and time-dependent specific internalization by different cellular models of atherosclerosis. Also, HRRAP NP combination therapy showed an efficient synergetic anti-atherosclerotic effect in vitro by effectively inhibiting the inflammatory response and oxidative stress in inflammatory cells. More importantly, HR NPs specifically accumulated in the atherosclerotic plaques of apolipoprotein E-deficient (ApoE-/-) mice, by active interaction with HA receptors overexpressed by different cells of the plaque. The treatment with HRRAP NPs remarkably inhibited the progression of atherosclerosis in ApoE-/- mice which resulted in stable plaques with considerably smaller necrotic cores, lower matrix metalloproteinase-9, and decreased proliferation of macrophages and smooth muscle cells (SMCs). Furthermore, HRRAP NPs attenuated RAP adverse effects and exhibited a good safety profile after long-term treatment in mice. Consequently, the developed pH-sensitive HRRAP NP represent a promising nanoplatform for atherosclerosis combination therapy.

Development and biomechanical test of a new pedicle screw for thoracolumbar spinal surgery.

Rupture of the medial pedicle wall often occurs during pedicle screw insertion. This allows the pedicle screw to compress or cut the nerve root and/or spinal cord. In this paper, we designed a new double-threaded pedicle screw that has a cylindrical outer diameter and a conical core diameter, with a wide thread at the front, no thread in the middle, and a narrow thread at the rear, according to an analysis of the shortcomings of the conventional pedicle screw and anatomical parameters in 300 healthy adult volunteers. After the screw was placed, the non-threaded portion of the screw was located at the vertebral pedicle. No nerve root cutting occurred if the screw was misplaced and the medial wall of the vertebral pedicle was broken. We then performed biomechanical tests using a static universal testing machine and compared the new double-threaded screws with the conventional full-threaded pedicle screws, however, the differences were not obvious. In compression bending fatigue tests, the novel double-threaded pedicle screws were subjected to 5 million fatigue cycle loads without failure. The current study demonstrated that the new pedicle screw possesses similar biomechanical features as those of the conventional fully threaded pedicle screw. This provides a basis for further clinical applications.

Unveiling the visible-light-driven photodegradation pathway and products toxicity of tetracycline in the system of Pt/BiVO4 nanosheets.

The antibiotics pollution has currently captured increasing concerns due to its potential hazards to the environment and human health. The development of efficient and viable techniques for the removal of antibiotics is one of the research hotspots in fields of wastewater treatment and pharmaceutical industry. Although the photodegradation of antibiotics is widely studied, the evolution and toxicity of degradation intermediates have been rarely documented. Herein, Pt nanoparticles (NPs) decorated BiVO4 nanosheets (Pt/BiVO4 NSs) that exhibit excellent tetracycline (TC) photodegradation activity and stability have been prepared. Especially, the TC degradation efficiency reaches ca. 88.5% after 60 min under visible light irradiation, which is superior to most of the metal loaded two-dimensional photocatalysts reported hitherto. The excellent photocatalytic activity is attributable to the enhanced light absorption capacity and charge separation efficiency in Pt/BiVO4 NSs. h+, •O2- and •OH are the main active species for TC degradation, resulting in three possible degradation pathways. Furthermore, we first verify that TC solutions treated by Pt/BiVO4 NSs are harmless to Escherichia coli K-12 and various bacteria in natural rivers, which would not stimulate Escherichia coli to produce antibiotics resistance genes (ARGs). This work develops an environmentally friendly photodegradation strategy using Pt/BiVO4 NSs with potentials for efficient remediation of antibiotics pollution in wastewater.

Paeoniflorin Regulates NEDD4L/STAT3 Pathway to Induce Ferroptosis in Human Glioma Cells.

Background: Paeoniflorin is an active component of a widely used traditional Chinese medicine with antitumor activity through ferroptosis induction. It has been reported recently that ferroptosis is emerging in certain types of cancer; however, its relevance in glioma is still not well studied. Methods: CCK8 assay was performed for cell proliferation. Expression of mRNA and protein was tested by qPCR and western blot, respectively. Clinical section samples were detected by IHC. The relationship between NEDD4L and STAT3 was validated by a coimmunoprecipitation assay. Apoptosis was identified by TUNEL assay. A xenograft mouse model was utilized to validate the potential of paeoniflorin toward glioma cancer cells. Results: The data suggested that paeoniflorin could increase NEDD4L expression in glioma cells. The NEDD4L expression level was lower in glioma cancer tissues compared to adjacent normal tissues, and it correlates with poor prognosis. Meanwhile, NEDD4L mediates the ubiquitination of STAT3. Furthermore, increased NEDD4L significantly inhibited cell viability and induced accumulation of intracellular ROS levels, accompanied by decreased expression of key ferroptosis factors Nrl2 and GPX4, while NEDD4L knockdown had a reverse effect, suggesting that ferroptosis could be involved. NEDD4L-induced ferroptosis could be rescued by forced expression of STAT3. A xenograft nude mouse model showed that paeoniflorin inhibits tumor growth and further sensitizes glioma cells to RSL3, another well-known ferroptosis inducer. Conclusions: In summary, this study demonstrated that paeoniflorin might function as an effective drug for glioma by inducing ferroptosis via upregulation of NEDD4L and repression of Nrl2, GPX4, and STAT3.

Association of gestational anemia with pregnancy conditions and outcomes: A nested case-control study.

BACKGROUND: Gestational anemia is a serious public health problem that affects pregnant women worldwide. Pregnancy conditions and outcomes might be associated with the presence of gestational anemia. This study investigated the association of pregnancy characteristics with anemia, exploring the potential etiology of the disease. AIM: To assess the association of pregnancy parameters with gestational anemia. METHODS: A nested case-control study was conducted based on the Chinese Pregnant Women Cohort Study-Peking Union Medical College Project (CPWCS-PUMC). A total of 3172 women were included. Patient characteristics and gestational anemia occurrence were extracted, and univariable and multivariable logistic regression models were used to analyze the association of pregnancy parameters with gestational anemia. RESULTS: Among the 3172 women, 14.0% were anemic, 46.4% were 25-30 years of age, 21.9% resided in eastern, 15.7% in middle, 12.4% in western 18.0% in southern and 32.0% in northern regions of China. Most women (65.0%) had a normal prepregnancy body mass index. Multivariable analysis found that the occurrence of gestational anemia was lower in the middle and western regions than that in the eastern region [odds ratio (OR) = 0.406, 95% confidence interval (CI): 0.309-0.533, P < 0.001)], higher in the northern than in the southern region (OR = 7.169, 95%CI: 5.139-10.003, P < 0.001), lower in full-term than in premature births (OR = 0.491, 95%CI: 0.316-0.763, P = 0.002), and higher in cases with premature membrane rupture (OR=1.404, 95%CI: 1.051-1.876, P = 0.02). CONCLUSION: Gestational anemia continues to be a health problem in China, and geographical factors may contribute to the situation. Premature birth and premature membrane rupture may be associated with gestational anemia. Therefore, we should vigorously promote local policy reformation to adapt to the demographic characteristics of at-risk pregnant women, which would potentially reduce the occurrence of gestational anemia.

Construction of the Gypsum-Coated Scaffolds for In Situ Bone Regeneration.

It is significant to use functional biomaterials to rationally engineer microenvironments for in situ bone regeneration in the field of bone tissue engineering. To this end, we constructed the gypsum-coated ß-tricalcium phosphate (G-TCP) scaffolds by combing a three-dimensional printing technique and an epitaxial gypsum growth method. In vitro simulation experiments showed that the as-prepared scaffolds could establish a dynamic and weakly acidic microenvironment in a simulated body liquid, in which the pH and the calcium ion concentration always changed due to the gypsum degradation and growth of bone-like apatite nanoplates on the scaffold surfaces. The cell experiments confirmed that the microenvironment established by the G-TCP surfaces promoted rapid osteogenic differentiation and proliferation of bone marrow mesenchymal stem cells (BM-MSCs). In vivo experiments confirmed that the G-TCP scaffolds had high bioactivity in modulating in situ regeneration of bone, and the bioactivity of the G-TCP scaffolds was endowed by correct pore structures, degradation of gypsum, and growth of a bone-like apatite layer. The microenvironment established by the gypsum degradation could stimulate tissue inflammation and recruit white blood cells and BM-MSCs and thus accelerating native healing cascades of the bone defects via a bone growth/remodeling-absorption cycle process. Furthermore, in vivo experiments demonstrated that after the bone defects had healed completely, the as-prepared scaffolds also degraded completely within 24 weeks.