Demystifying heparan sulfate-protein interactions.

Numerous proteins, including cytokines and chemokines, enzymes and enzyme inhibitors, extracellular matrix proteins, and membrane receptors, bind heparin. Although they are traditionally classified as heparin-binding proteins, under normal physiological conditions these proteins actually interact with the heparan sulfate chains of one or more membrane or extracellular proteoglycans. Thus, they are more appropriately classified as heparan sulfate-binding proteins (HSBPs). This review provides an overview of the various modes of interaction between heparan sulfate and HSBPs, emphasizing biochemical and structural insights that improve our understanding of the many biological functions of heparan sulfate.

Thinning by cluster breaking: Active matter and shear flows share thinning mechanisms.

Among many unexpected phenomena of active matter is the recently observed superfluid-like thinning (viscosity drop) behavior of bacteria suspensions. Understanding this peculiar self-propelled thinning by active matter is of theoretical and practical importance. Here, we find that, although distinct in driving mechanisms, active matter and shear flows exhibit similar thinning behaviors upon the increase of self-propulsion and shear forces, respectively. Our structural characterizations reveal that they actually share the same cluster-breaking mechanism of thinning. How fast and how shattered the cluster is broken determines the (dis)continuity of the thinning. This explains why adding active particles to Newtonian fluids can cause thinning, in which rotation of active particles play a key role in breaking clusters. Our work proposes a mechanism of self-propelled thinning and further establishes the underlying connections between active matter and shear flows.

Discontinuous instabilities in disordered solids.

Under a sufficiently large load, a solid material will flow via rearrangements, where particles change neighbors. Such plasticity is most easily described in the athermal, quasistatic limit of zero temperature and infinitesimal loading rate, where rearrangements occur only when the system becomes mechanically unstable. For disordered solids, the instabilities marking the onset of rearrangements have long been believed to be fold instabilities, in which an energy barrier disappears and the frequency of a normal mode of vibration vanishes continuously. Here, we report that there exists another, anomalous, type of instability caused by the breaking of a "stabilizing bond," whose removal creates an unstable vibrational mode. For commonly studied systems, such as those with harmonic finite-range interparticle interactions, such "discontinuous instabilities" are not only inevitable, they often dominate the modes of failure. Stabilizing bonds are a subset of all the bonds in the system and are prevalent in disordered solids generally. Although they do not trigger discontinuous instabilities in systems with vanishing stiffness at the interaction cutoff, they are, even in those cases, local indicators of incipient mechanical failure. They therefore provide an accurate structural predictor of instabilities not only of the discontinuous type but of the fold type as well.

Using heparan sulfate octadecasaccharide (18-mer) as a multi-target agent to protect against sepsis.

Sepsis is a lethal syndrome manifested by an unregulated, overwhelming inflammation from the host in response to infection. Here, we exploit the use of a synthetic heparan sulfate octadecasaccharide (18-mer) to protect against sepsis. The 18-mer not only inhibits the pro-inflammatory activity of extracellular histone H3 and high mobility group box 1 (HMGB1), but also elicits the anti-inflammatory effect from apolipoprotein A-I (ApoA-I). We demonstrate that the 18-mer protects against sepsis-related injury and improves survival in cecal ligation and puncture mice and reduces inflammation in an endotoxemia mouse model. The 18-mer neutralizes the cytotoxic histone-3 (H3) through direct interaction with the protein. Furthermore, the 18-mer enlists the actions of ApoA-I to dissociate the complex of HMGB1 and lipopolysaccharide, a toxic complex contributing to cell death and tissue damage in sepsis. Our study provides strong evidence that the 18-mer mitigates inflammatory damage in sepsis by targeting numerous mediators, setting it apart from other potential therapies with a single target.

A multiomic study uncovers a bZIP23-PER1A-mediated detoxification pathway to enhance seed vigor in rice.

Seed vigor in crops is important in terms of improving grain quality and germplasm conservation; however, little is known about its regulatory mechanisms through the encoded proteome and gene network. Comparative analyses of transcriptome (RNA sequencing [RNA-seq]) and broadly targeted metabolic profiling of two subspecific rice cultivars with distinct seed vigor during accelerated aging revealed various biological pathways and metabolic processes as key influences explaining trait differences. RNA-seq coexpression regulatory network analyses identified several transcription factors, including bZIP23 and bZIP42, that act as nodes in the gene network. Importantly, transgenic seeds of overexpression of bZIP23 enhanced seed vigor, whereas its gene knockout reduced seed vigor, suggesting that the protein it encodes functions as a positive regulator. Similarly, overexpression and knockout of PER1A that encodes a key player in the detoxification pathway enhanced and decreased seed vigor, respectively. We further demonstrated a direct interaction of the PER1A promoter with bZIP23 in seeds, which activates the expression of PER1A, and the genetic evidence suggested that bZIP23 most likely functions in a common pathway with and acts upstream of PER1A to modulate seed vigor. In addition, the control of seed vigor by the bZIP23-PER1A module was connected with that of the abscisic acid signaling pathway. Collectively, we revealed the genetic architecture of variation in seed vigor and uncovered the bZIP23-PER1A-mediated detoxification pathway that enhances the trait in rice.

IFT80 negatively regulates osteoclast differentiation via association with Cbl-b to disrupt TRAF6 stabilization and activation.

Excess bone loss due to increased osteoclastogenesis is a significant clinical problem. Intraflagellar transport (IFT) proteins have been reported to regulate cell growth and differentiation. The role of IFT80, an IFT complex B protein, in osteoclasts (OCs) is completely unknown. Here, we demonstrate that deletion of IFT80 in the myeloid lineage led to increased OC formation and activity accompanied by severe bone loss in mice. IFT80 regulated OC formation by associating with Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) to promote protein stabilization and proteasomal degradation of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6). IFT80 knockdown resulted in increased ubiquitination of Cbl-b and higher TRAF6 levels, thereby hyperactivating the receptor activator of nuclear factor-κß (NF-κß) ligand (RANKL) signaling axis and increased OC formation. Ectopic overexpression of IFT80 rescued osteolysis in a calvarial model of bone loss. We have thus identified a negative function of IFT80 in OCs.

Targeting the heparan sulfate-binding site of RAGE with monoclonal antibodies.

Heparan sulfate (HS) plays its biological functions by interacting with hundreds of secreted extracellular and transmembrane proteins. Interaction with HS has been shown to be required for the normal function of many HS-binding proteins. Receptor for advanced glycation end-product (RAGE) is such a protein, whose activation requires HS-induced oligomerization. Using RAGE as an exemplary protein, we show here the workflow of a simple method of developing and characterizing mAbs that targets the HS-binding site. We found that HS-binding site of RAGE is quite immunogenic as 18 out of 94 anti-RAGE mAbs target various epitopes within the HS-binding site. Sequence analysis found that a common feature of anti-HS-binding site mAbs is the presence of abundant acidic residues (range between 6 to 11) in the complementarity determining region, suggesting electrostatic interaction plays an important role in promoting antigen-antibody interaction. Interestingly, mAbs targeting different epitopes within the HS-binding site blocks HS-RAGE interaction to different degrees, and the inhibitory effect is highly consistent among mAbs that target the same epitope. Functional assay revealed that anti-HS-binding site mAbs show different potency in inhibiting osteoclastogenesis, and the inhibitory potency does not have a simple correlation with the affinity and the epitope. Our study demonstrates that developing HS-binding site targeting mAbs should be applicable to most HS-binding proteins. By targeting this unique functional site, these mAbs might find therapeutic applications in treating various human diseases.

Controlling Molecular Photoisomerization in Photonic Cavities through Polariton Funneling.

Strong coupling between photonic modes and molecular electronic excitations, creating hybrid light-matter states called polaritons, is an attractive avenue for controlling chemical reactions. Nevertheless, experimental demonstrations of polariton-modified chemical reactions remain sparse. Here, we demonstrate modified photoisomerization kinetics of merocyanine and diarylethene by coupling the reactant's optical transition with photonic microcavity modes. We leverage broadband Fourier-plane optical microscopy to noninvasively and rapidly monitor photoisomerization within microcavities, enabling systematic investigation of chemical kinetics for different cavity-exciton detunings and photoexcitation conditions. We demonstrate three distinct effects of cavity coupling: first, a renormalization of the photonic density of states, akin to a Purcell effect, leads to enhanced absorption and isomerization rates at certain wavelengths, notably red-shifting the onset of photoisomerization. This effect is present under both strong and weak light-matter couplings. Second, kinetic competition between polariton localization into reactive molecular states and cavity losses leads to a suppression of the photoisomerization yield. Finally, our key result is that in reaction mixtures with multiple reactant isomers, exhibiting partially overlapping optical transitions and distinct isomerization pathways, the cavity resonance can be tuned to funnel photoexcitations into specific reactant isomers. Thus, upon decoherence, polaritons localize into a chosen isomer, selectively triggering the latter's photoisomerization despite initially being delocalized across all isomers. This result suggests that careful tuning of the cavity resonance is a promising avenue to steer chemical reactions and enhance product selectivity in reaction mixtures.

Neuroprotection by tetramethylpyrazine and its synthesized analogues for central nervous system diseases: a review.

BACKGROUND: Due to the global increase in aging populations and changes in modern lifestyles, the prevalence of neurodegenerative diseases, cerebrovascular disorders, neuropsychiatrcic conditions, and related ailments is rising, placing an increasing burden on the global public health system. MATERIALS AND METHODS: All studies on tetramethylpyrazine (TMP) and its derivatives were obtained from reputable sources such as PubMed, Elsevier, Library Genesis, and Google Scholar. Comprehensive data on TMP and its derivatives was meticulously compiled. RESULTS: This comprehensive analysis explains the neuroprotective effects demonstrated by TMP and its derivatives in diseases of the central nervous system. These compounds exert their influence on various targets and signaling pathways, playing crucial roles in the development of various central nervous system diseases. Their multifaceted mechanisms include inhibiting oxidative damage, inflammation, cell apoptosis, calcium overload, glutamate excitotoxicity, and acetylcholinesterase activity. CONCLUSION: This review provides a brief summary of the most recent advancements in research on TMP and its derivatives in the context of central nervous system diseases. It involves synthesizing analogs of TMP and evaluating their effectiveness in models of central nervous system diseases. The ultimate goal is to facilitate the practical application of TMP and its derivatives in the future treatment of central nervous system diseases.

Dissociation of drug and negative emotional cue induced attentional bias in individuals with methamphetamine-use disorder.

BACKGROUND AND OBJECTIVES: Although both drugs and negative emotions can trigger drug craving or relapse in individuals with methamphetamine-use disorder (MUD), it remains unclear whether individuals with MUD have attentional biases toward both drug and negative emotional cues and whether this bias involves attention orientation or difficulty in attention disengagement. This study aimed to measure different components of attentional bias toward drug-related and negative emotional cues in individuals with MUD. METHODS: Two dot-probe tasks were used to investigate attentional bias toward drug (drug task) and negative emotional cues (emotion task) in individuals with MUD. Forty-three males with MUD (average age of 43.44 ± 11.91 years, average drug-use duration of 11.35 ± 8.39 years) participated in the study voluntarily. RESULTS: There was a significant interaction between the task type and location (p = .01). Specifically, for drug cues, participants showed significant difficulty in attention disengagement toward drug cues (p = .01); however, no attention orientation (p = .46). For negative emotional cues, neither significant attention orientation (p = .07) nor significant difficulty in attention disengagement (p = .50) was found. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Attentional bias in individuals with MUD was highly selective for drug cues; thus, difficulty in attention disengagement from drug cues can be considered a potential mediating mechanism for attentional bias modification interventions for individuals with MUD. This study served to generate hypotheses or suggest future experiments on interventions for individuals with MUD.

Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis.

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.

Microscopic Theory of Multimode Polariton Dispersion in Multilayered Materials.

We develop a microscopic theory for the multimode polariton dispersion in materials coupled to cavity radiation modes. Starting from a microscopic light-matter Hamiltonian, we devise a general strategy for obtaining simple matrix models of polariton dispersion curves based on the structure and spatial location of multilayered 2D materials inside the optical cavity. Our theory exposes the connections between seemingly distinct models that have been employed in the literature and resolves an ambiguity that has arisen concerning the experimental description of the polaritonic band structure. We demonstrate the applicability of our theoretical formalism by fabricating various geometries of multilayered perovskite materials coupled to cavities and demonstrating that our theoretical predictions agree with the experimental results presented here.

Optical Imaging of Ultrafast Phonon-Polariton Propagation through an Excitonic Sensor.

Hexagonal boron nitride (hBN) hosts phonon polaritons (PhP), hybrid light-matter states that facilitate electromagnetic field confinement and exhibit long-range ballistic transport. Extracting the spatiotemporal dynamics of PhPs usually requires "tour de force" experimental methods such as ultrafast near-field infrared microscopy. Here, we leverage the remarkable environmental sensitivity of excitons in two-dimensional transition metal dichalcogenides to image PhP propagation in adjacent hBN slabs. Using ultrafast optical microscopy on monolayer WSe2/hBN heterostructures, we image propagating PhPs from 3.5 K to room temperature with subpicosecond and few-nanometer precision. Excitons in WSe2 act as transducers between visible light pulses and infrared PhPs, enabling visible-light imaging of PhP transport with far-field microscopy. We also report evidence of excitons in WSe2 copropagating with hBN PhPs over several micrometers. Our results provide new avenues for imaging polar excitations over a large frequency range with extreme spatiotemporal precision and new mechanisms to realize ballistic exciton transport at room temperature.

Benefits evaluation of ecological restoration projects based on value realization of ecological products.

Ecological restoration project is the premise to realize the value of ecological products. The current ecological product value accounting and ecological restoration project benefit evaluation methods are interlinked. The benefit evaluation of ecological restoration projects can not only analyze the completion of ecological restoration projects, but also quantify the impact of externalities on regional development. This study proposes a hypothesis that the benefit evaluation results of ecological restoration projects can affect the realization of urban ecological product value. In order to verify the above hypothesis, this study designed a benefit evaluation framework to evaluate the economic benefits, ecological benefits and project costs of ecological restoration projects. In this study, the benefit evaluation results are divided into three cases to calculate the benefit-cost ratio under different conditions. The three cases are only considering the direct economic benefits (DEB), considering the indirect economic benefits (TEB) and considering the comprehensive benefits (AEB). Taking Jiangyin City of Jiangsu Province as an example, the benefit evaluation of water source protection project in Jiangyin City is carried out. The results show that the benefit-cost ratios in the three cases are 6.68,7.60 and 9.36, respectively. The results show that the benefit-cost ratio is different in different benefit situations. Therefore, when discussing the realization path of ecological product value in ecological restoration areas, it is also necessary to discuss the situation. The evaluation system can provide reference for the benefit evaluation of ecological restoration projects, and also provide data and theoretical support for the realization of regional ecological product value.

Management of an Isolated Left Vertebral Artery on the Arch During Zone 2 Landing Thoracic Endovascular Aortic Repair: A Multicentre Retrospective Study.

OBJECTIVE: To compare the early and midterm outcomes of three different strategies for an isolated left vertebral artery on the arch (LVoA) revascularisation during thoracic endovascular aortic repair (TEVAR) with a proximal zone 2 landing. METHODS: Between January 2016 and December 2021, 67 patients with LVoA and aortic arch pathologies who underwent zone 2 landing TEVAR at four medical centres were enrolled. These patients were divided into three groups for comparison: the novel chimney (group A, n = 28) with the right brachial-left brachial through and through (RLT) procedure; in vitro fenestration (group B, n = 24); and transposition (group C, n = 15). The flow direction and velocity of the LVoA was examined by Doppler ultrasound in the pre-, intra-, and post-operative periods. Primary outcomes were all cause mortality and new neurological symptoms. RESULTS: No deaths or new neurological symptoms occurred within 30 days. Early type Ia endoleak rates were 18% (n = 5), 17% (n = 4), and 0% in groups A, B, and C, respectively (p = .22). All patients had antegrade flow of the LVoA. The mean ± standard deviation duration of follow up was 63.6 ± 4.0 months. No deaths were observed during follow up. The rates of new neurological symptoms were 0%, 8%, and 33% in groups A, B, and C, respectively. The rates of midterm type Ia endoleak were 7%, 12%, and 0% in groups A, B, and C, respectively (p = .35). Bidirectional flow rates in the LVoA were 0%, 21%, and 27% in groups A, B, and C, respectively (p = .021). Two (8%) and three (20%) patients in groups B and C underwent a secondary procedure because of mild dizziness, but this was not necessary in group A (p = .058). CONCLUSION: The novel chimney technique of the RLT procedure may be feasible for patients with a LVoA requiring zone 2 anchoring. Accurate determination of the safety and feasibility of this novel technique requires larger sample sizes and longer follow up.

16S rRNA gene sequencing and machine learning reveal correlation between drug abuse and human host gut microbiota.

Over the past few years, there has been increasing evidence highlighting the strong connection between gut microbiota and overall well-being of the host. This has led to a renewed emphasis on studying and addressing substance use disorder from the perspective of brain-gut axis. Previous studies have suggested that alcohol, food, and cigarette addictions are strongly linked to gut microbiota and faecal microbiota transplantation or the use of probiotics achieved significant efficacy. Unfortunately, little is known about the relationship between drug abuse and gut microbiota. This paper aims to reveal the potential correlation between gut microbiota and drug abuse and to develop an accurate identification model for drug-related faeces samples by machine learning. Faecal samples were collected from 476 participants from three regions in China (Shanghai, Yunnan, and Shandong). Their gut microbiota information was obtained using 16S rRNA gene sequencing, and a substance use disorder identification model was developed by machine learning. Analysis revealed a lower diversity and a more homogeneous gut microbiota community structure among participants with substance use disorder. Bacteroides, Prevotella_9, Faecalibacterium, and Blautia were identified as important biomarkers associated with substance use disorder. The function prediction analysis revealed that the citrate and reductive citrate cycles were significantly upregulated in the substance use disorder group, while the shikimate pathway was downregulated. In addition, the machine learning model could distinguish faecal samples between substance users and nonsubstance users with an AUC = 0.9, indicating its potential use in predicting and screening individuals with substance use disorder within the community in the future.

Is laparoscopic surgery a preferred option for benign conditions in the caudate lobe of the liver?

BACKGROUND/AIM: Laparoscopic hepatectomy has become a common management strategy for liver tumors owing to its less invasive nature and enhanced visual perspective. Yet, its use in the caudate lobe poses challenges. This study evaluates the experiences of patients who underwent laparoscopic hepatectomy for hepatic tumors in the caudate lobe and aims to propose strategies for performing such procedures. METHODS: We retrospectively analyzed the clinical data of twelve patients who underwent laparoscopic hepatic caudate lobe resection at the Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Kunming Medical University. RESULTS: All twelve laparoscopic procedures were successful, with none requiring conversion to open surgery. The surgical methods varied: five cases involved simple resection of the Spiegel lobe, one case involved total caudate lobe resection, three cases involved paravena cava lobe resection, and three cases involved resection of the caudate process. The operation time ranged from 49 to 319 min (mean, 219 min). Intraoperative blood loss ranged from 20 to 500 ml, averaging 194 ml. No patients needed blood transfusions during or after the operation, and there were no instances of postoperative bleeding, bile leakage, or abdominal infection. CONCLUSION: Given adequate control of hepatic inflow, sufficient exposure to the surgical field, and an appropriate approach, laparoscopic hepatectomy in the caudate lobe could potentially become a standard surgical technique.

Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site.

Osteoprotegerin (OPG), a secreted decoy receptor for receptor activator of nuclear factor B ligand (RANKL), plays an essential role in regulating bone resorption. While much is known about the function of the N-terminal domains of OPG, which is responsible for binding to RANKL, the exact biological functions of the three C-terminal domains of OPG remain uncertain. We have previously shown that one likely function of the C-terminal domains of OPG is to bind cell surface heparan sulfate (HS), but the in vivo evidence was lacking. To investigate the biological significance of OPG-HS interaction in bone remodeling, we created OPG knock-in mice (opgAAA ). The mutated OPG is incapable of binding to HS but binds RANKL normally. Surprisingly, opgAAA/AAA mice displayed a severe osteoporotic phenotype that is very similar to opg-null mice, suggesting that the antiresorption activity of OPG requires HS. Mechanistically, we propose that the HS immobilizes secreted OPG at the surface of osteoblasts lineage cells, which facilitates binding of OPG to membrane-anchored RANKL. To further support this model, we altered the structure of osteoblast HS genetically to make it incapable of binding to OPG. Interestingly, osteocalcin-Cre;Hs2stf/f mice also displayed osteoporotic phenotype with similar severity to opgAAA/AAA mice. Combined, our data provide strong genetic evidence that OPG-HS interaction is indispensable for normal bone homeostasis.

Outcomes of U-shaped internal fixation in the treatment of avulsion fracture of calcaneal tubercle.

BACKGROUND: The purpose of this study was to analyze the efficacy of U-shaped internal fixation for calcaneal tubercle fracture after nearly 3 years of case follow-up and data collection. METHOD: We retrospectively analyzed the collected data from 16 patients with avulsion fracture of calcaneal tubercle between December 2018 and February 2021 at our institute. All patients were required to conform to regular follow up postoperatively. X-ray film was applied to all cases. The American Orthopaedic Foot and Ankle Association (AOFAS) score, Cedell score and the visual analog scale (VAS) were used to evaluate functional results. RESULTS: All patients achieved bone union. The preoperative AOFAS score was 26.34 ± 3.34, which was significantly different from 91.38 ± 6.15 half a year after operation (p = 0.003). The preoperative Cedell score was 31.05 ± 4.18 and the score half a year after operation was 92.17 ± 5.39(p = 0.011). The VAS score was 8.91 ± 1.51 before operation and decreased to 0.58 ± 1.31 half a year after operation (p = 0.014). CONCLUSIONS: In the treatments of calcaneal tubercle fracture, U-shaped internal fixation is a new attempt. Through the short-term follow-up study, we found that its therapeutic effect is excellent, which is a recommended treatment in clinic.

The serum lipidomics reveal the action mechanism of Danggui-Yimucao herbal pair in abortion mice.

Medical abortion is a common medical procedure that women choose to terminate an unwanted pregnancy, but it often brings post-abortion complications. Danggui (Angelica sinensis Radix)-Yimucao (Leonuri Herba), as a herbal pair (DY) in clinical prescriptions of traditional Chinese medicine, is often used in the treatment of gynecological diseases and has the traditional functions of tonifying the blood, promoting blood circulation, removing blood stasis and regulating menstruation. In this study, serum lipidomics were adopted to dissect the mechanism of DY in promoting recovery after medical abortion. A total of 152 differential metabolites were screened by lipidomics. All metabolites were imported into MetaboAnalyst for analysis, and finally key metabolic pathways such as glycerophospholipid metabolism, linoleic acid metabolism and pentose and glucuronate interconversions were enriched. Our results indicated that metabolic disorders in abortion mice were alleviated by DY through glycerophospholipid metabolism, while prostaglandin and leukotriene metabolites might be the key targets of DY to promote post-abortion recovery.