Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

Efficacy of acupuncture in refractory irritable bowel syndrome patients: a randomized controlled trial.

Previous studies have confirmed that acupuncture for irritable bowel syndrome (IBS) provided an additional benefit over usual care alone. Therefore, we performed a multicenter, randomized, sham-controlled trial to assess the efficacy and safety of acupuncture versus sham acupuncture for refractory IBS in patients in the context of conventional treatments. Patients in the acupuncture and sham acupuncture groups received real or sham acupuncture treatment in 3 sessions per week for a total of 12 sessions. The primary outcome was a change in the IBS-Symptom Severity Scale (IBS-SSS) score from baseline to week 4. A total of 521 participants were screened, and 170 patients (85 patients per group) were enrolled and included in the intention-to-treat analysis. Baseline characteristics were comparable across the two groups. From baseline to 4 weeks, the IBS-SSS total score decreased by 140.0 (95% CI: 126.0 to 153.9) in the acupuncture group and 64.4 (95% CI: 50.4 to 78.3) in the sham acupuncture group. The between-group difference was 75.6 (95% CI: 55.8 to 95.4). Acupuncture efficacy was maintained during the 4-week follow-up period. There were no serious adverse events. In conclusion, acupuncture provided benefits when combined with treatment as usual, providing more options for the treatment of refractory IBS.

Regulated circRNA nuclear export in neuronal differentiation.

Multiple mechanisms have been reported for how circular RNAs (circRNAs) are exported to the cytoplasm. A recent paper by Cao et al. shows that export of a subset of circRNAs with (A)-rich motifs, including one with a clear function, is regulated during neuronal development via a novel mechanism.

Human gastric microbiota analysis of refractory H. pylori infection.

H. pylori infection is gaining increasing attention, but detailed investigations into its impact on gastric microbiota remain limited. We collected gastric mucosa samples from 47 individuals divided into three groups: 1. Group HP: patients with initial positive H. pylori infection (25 cases); 2. Group ck: H. pylori-negative patients (14 cases); 3. Group DiffHP: patients with refractory H. pylori infection (8 cases). The samples were analyzed using 16S rDNA sequencing and functional prediction with PICRUSt. Group HP showed differences in flora distribution and function compared to Group ck, while Group DiffHP overlapped with Group HP. The abundances of Aeromonas piscicola, Shewanella algae, Vibrio plantisponsor, Aeromonas caviae, Serratia marcescens, Vibrio parahaemolyticus, Microbacterium lacticum, and Prevotella nigrescens were significantly reduced in both Group DiffHP and Group HP compared to Group ck. Vibrio shilonii was reduced only in Group DiffHP compared to Group ck, while Clostridium perfringens and Paracoccus marinus were increased only in Group DiffHP. LEfSe analysis revealed that Clostridium perfringens and Paracoccus marinus were enriched, whereas Vibrio shilonii was reduced in Group DiffHP compared to Group ck at the species level. In individuals with refractory H. pylori infection, the gastric microbiota exhibited enrichment in various human diseases, organic systems, and metabolic pathways (amino acid metabolism, carbohydrate metabolism, transcription, replication and repair, cell cycle pathways, and apoptosis). Patients with multiple failed H. pylori eradication exhibited significant changes in the gastric microbiota. An increase in Clostridium perfringens and Paracoccus marinus and a decrease in Vibrio shilonii appears to be characteristic of refractory H. pylori infection.

Nano-Titanium Oxide-Coated Carbon Nanotubes for Photothermal Therapy in the Treatment of Colorectal Cancer.

Recent studies have shown that carbon nanotubes display good potential in tumor photothermal therapy. In this study, we aimed to investigate the therapeutic potential of nano-titanium oxide-coated multi-walled carbon nanotubes (MCNTs) against colorectal cancer (CRC). Firstly, we modified TiO2 nanosheets on the surface of MCNTs to obtain nano-TiO2-coated MCNTs. Next, we conducted cell compatibility validation on nano-TiO2-coated MCNTs, and found that nano-TiO2-coated MCNTs were safe within a certain concentration range (0∼200 µg/ml). Interestingly, nano-TiO2-coated MCNTs displayed a good killing effect in CRC cells under NIR laser irradiation. Subsequently, nano-TiO2-coated MCNTs markedly promoted the proapoptotic effects of NIR laser irradiation, and significantly inhibited the expression of cell cycle proteins CCNA1 and CCND1 in CRC cells under NIR laser irradiation, which indicated that nano-TiO2-coated MCNTs exerted anti-CRC effects under NIR laser irradiation by regulating cell apoptosis and cell cycle. Furthermore, nano-TiO2-coated MCNTs accelerated inhibitory effects on the AKT signaling pathway under NIR laser irradiation. Finally, a cell line-derived xenograft model was established, and the results showed that nano-TiO2-coated MCNTs significantly exhibited superior tumor-killing ability under NIR laser irradiation in vivo. Collectively, our results demonstrate that nano-TiO2-coated MCNTs with NIR laser irradiation may serve as an effective strategy for the treatment of CRC. This article is protected by copyright. All rights reserved.

The Microbiome Protocols eBook initiative: Building a bridge to microbiome research.

The Microbiome Protocols eBook (MPB) serves as a crucial bridge, filling gaps in microbiome protocols for both wet experiments and data analysis. The first edition, launched in 2020, featured 152 meticulously curated protocols, garnering widespread acclaim. We now extend a sincere invitation to researchers to participate in the upcoming 2nd version of MPB, contributing their valuable protocols to advance microbiome research.

Non-Invasive Self-Adaptive Information States' Acquisition inside Dynamic Scattering Spaces.

Pushing the information states' acquisition efficiency has been a long-held goal to reach the measurement precision limit inside scattering spaces. Recent studies have indicated that maximal information states can be attained through engineered modes; however, partial intrusion is generally required. While non-invasive designs have been substantially explored across diverse physical scenarios, the non-invasive acquisition of information states inside dynamic scattering spaces remains challenging due to the intractable non-unique mapping problem, particularly in the context of multi-target scenarios. Here, we establish the feasibility of non-invasive information states' acquisition experimentally for the first time by introducing a tandem-generated adversarial network framework inside dynamic scattering spaces. To illustrate the framework's efficacy, we demonstrate that efficient information states' acquisition for multi-target scenarios can achieve the Fisher information limit solely through the utilization of the external scattering matrix of the system. Our work provides insightful perspectives for precise measurements inside dynamic complex systems.

Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis.

BACKGROUD: Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC. MATERIALS AND METHODS: Two researchers individually searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant studies published until February 2024. The Newcastle-Ottawa Scale assessed study quality. Random effects model was used to compute the odds ratio and weighted mean difference (WMD). Poisson regression comparison of the number of surgeries (NLC) was required for ET and RT to reach the stable stage of the LC. Heterogeneity was measured using Cochran's Q. Publication bias was tested using funnel plots, and sensitivity analysis assessed findings robustness. Subgroup analysis was done by operation type and patient characteristics. RESULTS: This meta-analysis involved 33 studies. The drainage volume of ET was higher than that of RT (WMD=-17.56 [30.22, -4.49]). After reaching the NLC, the operation time of ET and RT was shortened (ET: WMD=28.15[18.04, 38.26]; RT: WMD=38.53[29.20, 47.86]). Other perioperative outcomes also improved to varying degrees. Notably, RT showed more refined central lymph node resection(5.67 vs. 4.71), less intraoperative bleeding (16.56 mL vs. 42.30 mL), and incidence of transient recurrent laryngeal nerve injury(24.59 vs. 26.77). The NLC of RT was smaller than that of ET(Incidence-rate ratios [IRR]=0.64[0.57, 0.72]). CUSUM analysis (ET: IRR=0.84[0.72, 0.99]; RT: IRR=0.55[0.44, 0.69]) or a smaller number of respondents (ET: IRR=0.26[0.15, 0.46]; RT: IRR=0.51[0.41, 0.63]) was associated with smaller NLC. In RT, transoral approach (IRR=2.73[1.96, 4.50]; IRR=2.48[1.61, 3.84]) and retroauricular approach (RAA) (IRR=2.13[1.26, 3.60]; IRR=1.78[1.04, 3.05]) had smaller NLC compared to bilateral axillo-breast and transaxillary approach (TAA). In ET, the NLC of RAA was smaller than that of TAA (IRR=1.61[1.04, 2.51]), breast approach(IRR=1.67[1.06, 2.64]), and subclavian approach(IRR=1.80[1.03, 3.14]). CONCLUSIONS: Rich surgical experience can improve surgical results of ET and RT. After reaching the NLC, the perioperative outcomes of RT are better than those of ET. Study subjects, surgical approaches, and analysis methods can affect NLC.

Polystyrene microplastics exacerbated the toxicity of okadaic acid to the small intestine in mice.

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 µg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1ß and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.

Sideroflexin-1 promotes progression and sensitivity to lapatinib in triple-negative breast cancer by inhibiting TOLLIP-mediated autophagic degradation of CIP2A.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and it lacks specific therapeutic targets and effective treatment protocols. By analyzing a proteomic TNBC dataset, we found significant upregulation of sideroflexin 1 (SFXN1) in tumor tissues. However, the precise function of SFXN1 in TNBC remains unclear. Immunoblotting was performed to determine SFXN1 expression levels. Label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry were used to identify the downstream targets of SFXN1. Mechanistic studies of SFXN1 and cellular inhibitor of PP2A (CIP2A) were performed using immunoblotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional experiments were used to investigate the role of SFXN1 in TNBC cells. SFXN1 was significantly overexpressed in TNBC tumor tissues and was associated with unfavorable outcomes in patients with TNBC. Functional experiments demonstrated that SFXN1 promoted TNBC growth and metastasis in vitro and in vivo. Mechanistic studies revealed that SFXN1 promoted TNBC progression by inhibiting the autophagy receptor TOLLIP (toll interacting protein)-mediated autophagic degradation of CIP2A. The pro-tumorigenic effect of SFXN1 overexpression was partially prevented by lapatinib-mediated inhibition of the CIP2A/PP2A/p-AKT pathway. These findings may provide a new targeted therapy for patients with TNBC.

High performance few-mode fiber-based light field direction sensing system using deep convolutional neural network: fiber speckle demodulation network (FSDNET).

Precisely sensing the light field direction information plays the essential role in the fields of three-dimensional (3D) imaging, light field sensing, target positioning and tracking, remote sensing, etc. It is thrilling to find that the optical fiber can be used as a sensing component due to its high sensitivity, compact size, and strong resistance to electromagnetic interference. According to the core principle that the few-mode fiber output speckle pattern is sensitive to the change of incident light field direction, the variation characteristics is further investigated in this research study. Based on the simulation and analysis of the fiber transmission characteristics, the output speckle corresponding to the incident light field with the direction in the range of ±6° horizontally and vertically are calculated. Furthermore, a deep convolutional neural network (CNN): fiber speckle demodulation network (FSDNET) is proposed and constructed to establish what we believe to be a novel way to reveal and identify the mapping relationship between the light field direction and the output speckle. The theoretical simulation shows that the mean absolute error (MAE) between the perceived light field directions and the true directions is 0.01°. Then, a light field direction sensing system based on the few-mode fiber is developed. Regarding to the performance of the sensing system, the MAE of the FSDNET for the light field directions that have appeared in the training set is 0.0389°, and for testing set of the unknown directions that have not appeared in the training set, the MAE is 0.0570°. Therefore, the simulation and experimental results prove that high performance sensing of light field direction can be achieved by the proposed few-mode fiber sensing system and the FSDNET.

[Relationship between DTA Mutations and Thromboembolism in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.

Archimedean Spirals with Controllable Chirality: Disk Substrate-Mediated Solution Assembly of Rod-Coil Block Copolymers.

Spirals are common in nature; however, they are rarely observed in polymer self-assembly systems, and the formation mechanism is not well understood. Herein, we report the formation of two-dimensional (2D) spiral patterns via microdisk substrate-mediated solution self-assembly of polypeptide-based rod-coil block copolymers. The spiral pattern consists of multiple strands assembled from the block copolymers, and two central points are observed. The spirals fit well with the Archimedean spiral model, and their chirality is dependent on the chirality of the polypeptide blocks. As revealed by a combination of experiments and theoretical simulations, these spirals are induced by an interplay of the parallel ordering tendency of the strands and circular confinement of the microdisks. This work presents the first example regarding substrate-mediated self-assembly of block copolymers into spirals. The gained information could not only enhance our understanding of natural spirals but also assist in both the controllable preparations and applications of spiral nanostructures.

The Growth-Promoting and Colonization of the Pine Endophytic Pseudomonas abietaniphila for Pine Wilt Disease Control.

In this study, we focused on evaluating the impact of Pseudomonas abietaniphila BHJ04 on the growth of Pinus massoniana seedlings and its biocontrol efficacy against pine wilt disease (PWD). Additionally, the colonization dynamics of P. abietaniphila BHJ04 on P. massoniana were examined. The growth promotion experiment showed that P. abietaniphila BHJ04 significantly promoted the growth of the branches and roots of P. massoniana. Pot control experiments indicated that strain BHJ04 significantly inhibited the spread of PWD. There were significant changes in the expression of several genes related to pine wood nematode defense in P. massoniana, including chitinase, nicotinamide synthetase, and triangular tetrapeptide-like superfamily protein isoform 9. Furthermore, our results revealed significant upregulation of genes associated with the water stress response (dehydration-responsive proteins), genetic material replication (DNA/RNA polymerase superfamily proteins), cell wall hydrolase, and detoxification (cytochrome P450 and cytochrome P450 monooxygenase superfamily genes) in the self-regulation of P. massoniana. Colonization experiments demonstrated that strain BHJ04 can colonize the roots, shoots, and leaves of P. massoniana, and the colonization amount on the leaves was the greatest, reaching 160,000 on the 15th day. However, colonization of the stems lasted longer, with the highest level of colonization observed after 45 d. This study provides a preliminary exploration of the growth-promoting and disease-preventing mechanisms of P. abietaniphila BHJ04 and its ability to colonize pines, thus providing a new biocontrol microbial resource for the biological control of plant diseases.

Fertilizer Effects on the Nitrogen Isotope Composition of Soil and Different Leaf Locations of Potted Camellia sinensis over a Growing Season.

The nitrogen-stable isotopes of plants can be used to verify the source of fertilizers, but the fertilizer uptake patterns in tea (Camellia sinensis) plants are unclear. In this study, potted tea plants were treated with three types of organic fertilizers (OFs), urea, and a control. The tea leaves were sampled over seven months from the top, middle, and base of the plants and analyzed for the δ15N and nitrogen content, along with the corresponding soil samples. The top tea leaves treated with the rapeseed cake OF had the highest δ15N values (up to 6.6‱), followed by the chicken manure, the cow manure, the control, and the urea fertilizer (6.5‱, 4.1‱, 2.2‱, and 0.6‱, respectively). The soil treated with cow manure had the highest δ15N values (6.0‱), followed by the chicken manure, rapeseed cake, control, and urea fertilizer (4.8‱, 4.0‱, 2.5‱, and 1.9‱, respectively). The tea leaves fertilized with rapeseed cake showed only slight δ15N value changes in autumn but increased significantly in early spring and then decreased in late spring, consistent with the delivery of a slow-release fertilizer. Meanwhile, the δ15N values of the top, middle, and basal leaves from the tea plants treated with the rapeseed cake treatment were consistently higher in early spring and lower in autumn and late spring, respectively. The urea and control samples had lower tea leaf δ15N values than the rapeseed cake-treated tea and showed a generalized decrease in the tea leaf δ15N values over time. The results clarify the temporal nitrogen patterns and isotope compositions of tea leaves treated with different fertilizer types and ensure that the δ15N tea leaf values can be used to authenticate the organic fertilizer methods across different harvest periods and leaf locations. The present results based on a pot experiment require further exploration in open agricultural soils in terms of the various potential fertilizer effects on the different variations of nitrogen isotope ratios in tea plants.

The Combination of Bacillus natto JLCC513 and Ginseng Soluble Dietary Fiber Attenuates Ulcerative Colitis by Modulating the LPS/TLR4/NF-κB Pathway and Gut Microbiota.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that is currently difficult to treat effectively. Both Bacillus natto (BN) and ginseng-soluble dietary fiber (GSDF) are anti-inflammatory and helps sustain the intestinal barrier. In this study, the protective effects and mechanism of the combination of B. natto JLCC513 and ginseng-soluble dietary fiber (BG) in DSS-induced UC mice were investigated. Intervention with BG worked better than taking BN or GSDF separately, as evidenced by improved disease activity index, colon length, and colon injury and significantly reduced the levels of oxidative and inflammatory factors (LPS, ILs, and TNF-α) in UC mice. Further mechanistic study revealed that BG protected the intestinal barrier integrity by maintaining the tight junction proteins (Occludin and Claudin1) and inhibited the LPS/TLR4/NF-κB pathway in UC mice. In addition, BG increased the abundance of beneficial bacteria such as Bacteroides and Turicibacter and reduced the abundance of harmful bacteria such as Allobaculum in the gut microbiota of UC mice. BG also significantly upregulated genes related to linoleic acid metabolism in the gut microbiota. These BG-induced changes in the gut microbiota of mice with UC were significantly correlated with changes in pathological indices. In conclusion, this study demonstrated that BG exerts protective effect against UC by regulating the LPS/TLR4/NF-κB pathway and the structure and metabolic function of gut microbiota. Thus, BG can be potentially used in intestinal health foods to treat UC.

Balance between FeIV-NiIV synergy and Lattice Oxygen Contribution for Accelerating Water Oxidation.

Hydrogen obtained from electrochemical water splitting is the most promising clean energy carrier, which is hindered by the sluggish kinetics of the oxygen evolution reaction (OER). Thus, the development of an efficient OER electrocatalyst using nonprecious 3d transition elements is desirable. Multielement synergistic effect and lattice oxygen oxidation are two well-known mechanisms to enhance the OER activity of catalysts. The latter is generally related to the high valence state of 3d transition elements leading to structural destabilization under the OER condition. We have found that Al doping in nanosheet Ni-Fe hydroxide exhibits 2-fold advantage: (1) a strong enhanced OER activity from 277 mV to 238 mV at 10 mA cm-2 as the Ni valence state increases from Ni3.58+ to Ni3.79+ observed from in situ X-ray absorption spectra. (2) Operational stability is strengthened, while weakness is expected since the increased NiIV content with 3d8L2 (L denotes O 2p hole) would lead to structural instability. This contradiction is attributed to a reduced lattice oxygen contribution to the OER upon Al doping, as verified through in situ Raman spectroscopy, while the enhanced OER activity is interpreted as an enormous gain in exchange energy of FeIV-NiIV, facilitated by their intersite hopping. This study reveals a mechanism of Fe-Ni synergy effect to enhance OER activity and simultaneously to strengthen operational stability by suppressing the contribution of lattice oxygen.

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies.

Hypoxia-inducible factor 1 alpha (HIF-1α) is a major molecular mediator of the hypoxic response. In the endometrium, local hypoxic conditions induced by hormonal fluctuations and endometrial vascular remodeling contribute to the production of HIF-1α, which plays an indispensable role in a series of physiological activities, such as menstruation and metamorphosis. The sensitive regulation of HIF-1α maintains the cellular viability and regenerative capacity of the endometrium against cellular stresses induced by hypoxia and excess reactive oxygen species. In contrast, abnormal HIF-1α levels exacerbate the development of various endometrial pathologies. This knowledge opens important possibilities for the development of promising HIF-1α-centered strategies to ameliorate endometrial disease. Nonetheless, additional efforts are required to elucidate the regulatory network of endometrial HIF-1α and promote the applications of HIF-1α-centered strategies in the human endometrium. Here, we summarize the role of the HIF-1α-mediated pathway in endometrial physiology and pathology, highlight the latest HIF-1α-centered strategies for treating endometrial diseases, and improve endometrial receptivity.