Two-Dimensional Semiconductors and Transistors for Future Integrated Circuits.

Silicon transistors are approaching their physical limit, calling for the emergence of a technological revolution. As the acknowledged ultimate version of transistor channels, 2D semiconductors are of interest for the development of post-Moore electronics due to their useful properties and all-in-one potentials. Here, the promise and current status of 2D semiconductors and transistors are reviewed, from materials and devices to integrated applications. First, we outline the evolution and challenges of silicon-based integrated circuits, followed by a detailed discussion on the properties and preparation strategies of 2D semiconductors and van der Waals heterostructures. Subsequently, the significant progress of 2D transistors, including device optimization, large-scale integration, and unconventional devices, are presented. We also examine 2D semiconductors for advanced heterogeneous and multifunctional integration beyond CMOS. Finally, the key technical challenges and potential strategies for 2D transistors and integrated circuits are also discussed. We envision that the field of 2D semiconductors and transistors could yield substantial progress in the upcoming years and hope this review will trigger the interest of scientists planning their next experiment.

Bushen Antai recipe alleviates embryo absorption by enhancing immune tolerance and angiogenesis at the maternal-fetal interface via mobilizing MDSCs in abortion-prone mice.

BACKGROUND: Recurrent pregnancy loss (RPL) is a tricky puzzle that disturbs female reproduction worldwide. According to previous research, Bushen Antai recipe (BAR), a classic Chinese herbal formula widely used in clinic for miscarriage, exhibited multifaceted benefits in improving embryo implantation and attenuating early pregnancy loss. Myeloid-derived suppressor cells (MDSCs), a set of immunoregulatory cells critical in inflammation balance, get growing attention for their indispensable role in successful pregnancy. PURPOSE: To investigate the therapeutic efficacy of BAR in abortion-prone mice and explore the potential mechanisms of BAR regarding MDSCs. METHODS: RPL mice (CBA/J females paired with DBA/2 males, BALB/c males were used as the control) were administered with BAR1 (5.7 g/kg), BAR2 (11.4 g/kg), progesterone (P4), or distilled water from embryo day (D) 0.5 until D10.5. The rate of embryo absorption on D10.5 and the health status of progeny were measured. The systemic inflammatory states and the placenta-uterus milieu were assessed by serum cytokine levels, placenta-uterus architecture, and related protein expression at the maternal-fetal interface. Flow cytometry analysis was carried out to measure the frequency of MDSCs. Furthermore, we established the MDSCs-depletion mouse model by using C57BL/6 females mated with BALB/c males via intraperitoneal injection of anti-Gr-1 antibody on D6.5, while irrelative LTF antibody was used as the control. Similarly, BAR1, BAR2, P4, or distilled water was separately applied. Embryo absorption rate, systemic inflammatory states, placenta-uterus milieu, and MDSCs frequency were evaluated as mentioned above. RESULTS: Significantly, embryo absorption rate was increased with disrupted placenta-uterus milieu and exorbitant proinflammatory cytokines in RPL mice, meanwhile, MDSCs number in the placenta-uterus unit were apparently reduced (⁎⁎⁎p < 0.001). BAR treatment markedly alleviated the poor conditions above and increased MDSCs number (####p < 0.0001). Flow cytometry analysis validated the efficacy of anti-Gr-1 antibody and the raised embryo absorption rate confirmed the essentiality of MDSCs in normal pregnancy (⁎⁎p < 0.01). Besides, the placenta-uterus milieu was destroyed, accompanied by the impaired expression of immune tolerance and angiogenesis related factors in the MDSCs-depletion mice. Even though, BAR treatment reversed the embryo resorption phenotype and optimized the serum cytokine milieu, mobilizing MDSCs and rejuvenating active intercellular communication. Thereby, BAR facilitated the expression of MDSCs-related functional molecules, promoting immune tolerance and vascular remodeling at the placenta-uterus unit. CONCLUSION: We unfurled the remarkable therapeutic ability of BAR in abortion-prone mice, and this was achieved by mobilizing MDSCs, thus favoring immune tolerance and angiogenesis at the maternal-fetal interface.

Investigation of differential levels of phosphorus fixation in dolomite and calcium carbonate amended red soil.

BACKGROUND: The pH adjustment of acidic red soils with lime materials is beneficial for the reduction of phosphorus (P) fixation. However, the reasons for varying levels of P activation after adding different lime materials have not been fully investigated. Therefore, this study examined changes in soil labile P and P forms after phosphate application to calcium carbonate (CaCO3 ) and dolomite amended red soil during a 120-day incubation period. Also change of P sorption properties in the amended soil samples from day 120 were examined through a sorption-desorption experiment. RESULTS: The increase of soil H2 O-P and NaHCO3 -P in the CaCO3 and dolomite amended soil treatments was mainly ascribed to the decline of the NaOH-P. However, when compared with the control treatment after 120 days, soil Olsen-P significantly increased by 34% and 66% in the CaCO3 and dolomite treatments. The Hedley P fractionation results demonstrated that the CaCO3 application caused a notable increase of HCl-P (stable Ca-P), which was 88.4% higher than that in the dolomite treatment. However, the formation of stable P was strongly suppressed in the dolomite treatment due to the presence of magnesium (Mg), which was identified by the negative relationship between M3-Mg and HCl-P. In line with these findings, P sorption-desorption work showed weaker P binding energy in the dolomite treatment relative to the CaCO3 treatment. CONCLUSION: In terms of increasing P availability in red soil, this study suggests that dolomite should be used to substitute CaCO3 in order to reduce the soil P fixation. © 2021 Society of Chemical Industry.

Bushen Huoxue recipe attenuates early pregnancy loss via activating endometrial COX2-PGE2 angiogenic signaling in mice.

BACKGROUND: During the fresh cycles of in vitro fertilization and embryo transfer, a disturbance in the reproductive endocrine environment following controlled ovarian hyperstimulation (COH) is closely related to compromised endometrial receptivity. This is a major disadvantage for women during pregnancy. Based on the theory of traditional Chinese medicine, Bushen Huoxue recipe (BSHXR) has been indicated to facilitate embryo implantation. METHODS: The COH model (Kunming breed) was induced by injecting mice with pregnant mare serum gonadotrophin (0.4 IU/g) and human chorionic gonadotropin (1 IU/g), followed by treatment with BSHXR at three different concentrations (5.7, 11.4, and 22.8 g/kg), Bushen recipe (BSR) (5.7 g/kg), and Huoxue recipe (HXR) (5.7 g/kg). After successful mating, the pregnancy rate and implantation sites were examined on embryo day 8 (ED8), and the weight ratio of endometrium was calculated on ED4 midnight. Serum estrogen, progesterone, and endometrial PGE2 levels were measured using enzyme-linked immunosorbent assay. The endometrial microvasculature was evaluated using CD31 immunostaining. The protein and mRNA levels of the angiogenic factors in the endometrium were evaluated using western blot, immunohistochemistry, and polymerase chain reaction. RESULTS: In the COH group, the pregnancy rate and implantation sites were significantly decreased, and abnormal serum hormone levels and impaired endometrial vascular development were observed. After BSHXR treatment, the supraphysiological serum progesterone level in COH mice was restored to normalcy. Moreover, the abnormal expression of the endometrial pro-angiogenic factors, including HIF1α, COX2-PGE2 pathway, and the down-stream factors, namely, MMP2, MMP9, TIMP2, and FGF2 after subjecting mice to COH was significantly improved after BSHXR treatment. CONCLUSION: BSHXR could improve embryo implantation by regulating hormonal balance and modulating endometrial angiogenesis in mice, without inducing any side effects in normal pregnancy.

Alum split applications strengthened phosphorus fixation and phosphate sorption in high legacy phosphorus calcareous soil.

High phosphorus (P) saturation arising from historic P inputs to protected vegetable fields (PVFs) drives high P mobilisation to waterbodies. Amendment of soils with alum has shown potential in terms of fixing labile P and protecting water quality. The present 15 month pot experiment investigated P stabilisation across single alum application (Alum-1 treatment, 20 g alum/kg soil incorporated into soil before the maize was sown), alum split applications (Alum-4 treatment, 5 g alum/kg soil incorporated into soil before each crop was sown i.e. 4 × 5 g/kg) and soil only treatment (Control). Results showed that the Alum-1 treatment caused the strongest stabilisation of soil labile P after maize plant removal, whereas the P stabilisation effect was gradually weakened due to the transformation of soil non-labile P to labile P and the reduced active Al3+ in soil solution. For the Alum-4 treatment, soil labile P decreased gradually with each crop planting and was lower than the Alum-1 treatment at the end of the final crop removal, without any impairment on plant growth. The better P stabilisation at the end of Alum-4 treatment was closely correlated with a progressive supply of Al3+ and a gradual decrease of pH, which resulted in higher contents of poorly-crystalline Al, Fe and exchangeable Ca. These aspects were conducive to increasing the soil P stabilisation and phosphate sorption. In terms of management, growers in continuous cropping systems could utilise split alum applications as a strategy to alleviate P losses in high-P enriched calcareous soil.

Oxymatrine loaded nitric oxide-releasing liposomes for the treatment of ulcerative colitis.

Oxymatrine (OM) is the biologically active ingredient of Chinese medicinal herb Sophora flavescens, which is reported to be effective on alleviating ulcerative colitis (UC) due to its anti-inflammatory property. However, its highly effective dose is an obstacles to its application. Therefore, liposome was used to encapsulate OM, realize targeting delivery to colitis and thus reduce drug dosage. Meanwhile, considering the potential anti-inflammatory ability of nitric oxide (NO), a NO donor, d-α-tocopheryl polyethylene glycol succinate nitrate (TN), was introduced into the liposomal system and OM loaded NO-releasing liposomes (OM@TN-lip) were prepared in order to co-deliver OM and NO to the inflammatory lesions of DSS-induced UC mice to achieve the combination therapy. OM@TN-lip was multilamelar sphere with the encapsulation efficiency of ~70%, the diameter of ~200 nm and ζ-potential of about -13 mV. Bio-distribution results revealed the liposomes could efficiently accumulate in the inflammatory colon by diffusion and maintain for more than 36 h. In UC mice model, OM@TN-lip showed significant alleviation of inflammation and the treatment was highly related to down-regulation of pro-inflammatory cytokines TNF-α, IFN-γ, IL-1ß and IL-6, decrease of macrophages infiltration, activity decrease of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), and rebuilding antioxidant/oxidation balance by reducing reactive oxygen species (ROS) and increasing Glutathione (GSH) in colon.

Understanding phosphate sorption characteristics of mineral amendments in relation to stabilising high legacy P calcareous soil.

In China, excessive phosphorus (P) application in protected vegetable fields has led to high legacy P stores. Soil amendment with alum or dolomite is one of many best management practices (BMPs) used to reduce P losses in calcareous soils. However, both the kinetics and mechanisms of P sorption and soil available P in amended soils are understudied. Herein, both aspects were looked at under controlled conditions. Firstly, a sorption study which coupled P concentrations with poorly-crystalline Al hydroxides and dolomite was conducted. Results from this batch experiment showed that P sorption on poorly-crystalline Al hydroxides was homogenous and occurred mainly via displacement of inner-sphere hydroxyl (Al-OH) instead of the formation of AlPO4. However, the amount of sorbed P reached maximum sorption of 73.1 mg g-1 and did not change with further increase in P concentration. It was observed that P adsorbed onto the dolomite surface at low P concentrations, whereas hydroxyl replacement and uneven cluster precipitation of Ca3(PO4)2 occurred at high P concentrations. A second 90 day incubation experiment investigated changes to soil available P and sorption-desorption across variable rates of amendments (0-50 g kg-1). Results showed that alum amendment at a rate of 50 g kg-1 decreased soil CaCl2-P and Olsen-P concentrations by 91.9% and 57.8%, respectively. However, Olsen-P increased when the dolomite rates were <20 g kg-1. Phosphorus sorption-desorption of the amended soil showed alum had higher P sorption efficiency than dolomite at low addition rates (<10 g kg-1). However, soil amended with high dolomite rates (>10 g kg-1) could sorb more P in comparison with alum when P concentrations were increased. The P status of the amended soil was closely connected to the P sorption mechanisms on mineral amendments, soil P concentrations and soil properties.

Bushen Huoxue Recipe Alleviates Implantation Loss in Mice by Enhancing Estrogen-Progesterone Signals and Promoting Decidual Angiogenesis Through FGF2 During Early Pregnancy.

Bushen Huoxue recipe (BSHXR) is a classic Chinese herbal prescription for nourishing the kidney and activating blood circulation. It consists of six herbs: Astragali radix, Angelicae sinensis radix, Ligustici Chuanxiong Rhizoma, Cuscutae semen, Taxilli Herba, and Dipsaci Radix, and the main active constituents of BSHXR are ferulic acid, calycosin-7-glucopyranoside, hyperoside, quercitrin, and asperosaponin VI. In clinical practice, BSHXR is traditionally used to treat failed pregnancy and its complications. However, little is known about the underlying mechanism of BSHXR for the treatment of implantation loss during early pregnancy. In the current study, controlled ovarian hyperstimulation was induced in mice as our implantation loss model, and we evaluated the effects of BSHXR on implantation, decidualization, decidual angiogenesis, and reproductive outcome. We showed that BSHXR could regulate the supraphysiological levels of serum estrogen and progesterone observed in these mice, and also act on estrogen and progesterone receptors in the stroma and epithelium. BSHXR also enhanced FGF2 expression in the vascular sinus folding area of the decidua, thus potentially reducing implantation loss during early pregnancy and contributing to placentation and survival of the fetuses. Taken together, our findings provide scientific evidence for the application of BSHXR in the clinic as a treatment for implantation loss during early pregnancy, and warrant further investigation of BSHXR as an effective treatment for failed pregnancy and its complications.

Effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation implantation dysfunction.

The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation (COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotrophin (PMSG), followed by 7.5 IU human chorionic gonadotrophin (HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group (NC), COH implantation dysfunction model group (COH), low dosage of Bu-Shen-An-Tai recipe group (LOW), middle dosage of Bu-Shen-An-Tai recipe group (MID) and high dosage of Bu-Shen-An-Tai recipe group (HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17ß-estradiol (E2) and progesterone (P4) were determined by radioimmunoassay (RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope (TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis- related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of E2 and P4, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It's helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.

Immunomodulatory mechanism of Bushen Huoxue Recipe alleviates cyclophosphamide-induced diminished ovarian reserve in mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Huoxue recipe (BHR) is a Chinese herbal prescription composed of ten herbs and it is widely used for the treatment of diminished ovarian reserve (DOR). This study investigates the potentially beneficial effects and underlying mechanism of BHR on a cyclophosphamide (CTX) induced model of DOR in mice. MATERIALS AND METHODS: Granules of BHR were first subjected to high performance liquid chromatography (HPLC) to determine the exact ingredients within the mixture. We then induced DOR in mice by injecting them with 90mg/kg of CTX. Following the single intraperitoneal injection, mice then received either saline or BHR for 21 days. To assess the effects of BHR on DOR, we examined splenic and ovarian morphology, estrous cycle duration, ovarian index, follicle number, body weight, and concentration of serum E2 and FSH. To explore the immunological mechanism behind the effects, mouse splenocytes were isolated in order to analyze the proportion of CD4+, CD8+ T cells and Th1, Th17 and Treg subsets by flow cytometry. The serum levels of IFN-γ, TNF-α, IL-4, IL-17A, IL-6 and IL-10 were detected using Cytometric Bead Array (CBA). Additionally, the mRNA expression levels of T-bet, RORγt and Foxp3 were measured with quantitative real-time PCR. RESULTS: Our results show that following treatment with BHR in DOR mice, several measures showed significant improvement. The morphology of the ovary and spleen, estrous cycle duration, body weight, ovarian index, and serum levels of E2 and FSH recovered to approximately normal levels and the loss of follicles at all stages was significantly attenuated. Furthermore, the elevated proportions of CD4+ T cells, Th1, Th17, Treg subsets and the increased serum levels of IFN-γ, TNF-α, IL-17A, IL-6 and IL-10 as well as the mRNA expressions of T-bet, RORγt and Foxp3 in DOR mice were significantly decreased. CONCLUSIONS: Our results show that BHR is a promising candidate to treat DOR mice and this beneficial effect may be mediated through the downregulation of augmented autoimmunity.

Effect and mechanism of Bushen Huoxue recipe on ovarian reserve in mice with premature ovarian failure.

The aim of the present study was to explore the effect and mechanism of Bushen Huoxue recipe (BHR) on ovarian reserve in mice with premature ovarian failure (POF). Mice were divided into 3 groups: normal group, model group and BHR group. Intraperitoneal injection of cyclophosphamide was performed to create the POF model. Primordial follicular (PDF) number, ovarian wet weight, ovarian index, and estrous cycle were analyzed to evaluate the effect of BHR on POF. Meanwhile, the mRNA and protein level of Mouse Vasa Homologue (MVH) in the bone marrow, peripheral blood and ovary were detected, to explore the underlying mechanism of the treatment efficacy of BHR on ovarian reserve. By the time of BHR treatment for 28 days, BHR increased the PDF number and shortened the estrous cycle of POF mice. BHR also decreased the mRNA level of MVH in the bone marrow, and increased mRNA and protein level of MVH in the ovary of POF mice. Our results demonstrated a treatment efficacy of BHR on POF mice, and revealed that BHR might repair the dysfunction of germline stem cells in the bone marrow, and thus to improve the ovarian reserve and enhance the ovarian function of POF mice through neo-oogenesis.

[Effect of Guishen Pill on expression levels of Oct-4, MVH, and Egr-1 in mice with diminished ovarian reserve].

OBJECTIVE: To study the effect of Guishen Pill (GSP) on expression levels of Oct-4, MVH, and Egr-1 in mice with diminished ovarian reserve (DOR). METHODS: Totally 40 female C57BL/6J mice were randomly divided into 4 groups, the normal control group, the model group, the GSP group, and the dehydroepiandrosterone (DHEA) group, 10 in each group. Pregnant mare serum gonadotropin (PMSG), human chorionic gonadotropin (HCG), and prostaglandin F2α (PGF2α) were sequentially administrated to produce superovulation. The DOR model was established by exposing to ozone inhalation. Mice in the GSP group were intragastrically administered with GSP at 0.3 mL. Those in the DHEA group were intragastrically administered with DHEA at 0.3 mL. Equal volume of normal saline was intragastrically administered to mice in the normal control group and the model group. All mice wer treated for 21 days. Serum levels of estrogen (E2), progestogen (P), and anti-Müllerian hormone (AMH) were measured by ELISA. Changes of Oct-4, anti-AMH, and early growth response gene-1 (Egr-1) mRNA in ovaries were dtected by Real-time PCR. RESULTS: Compared with the model group, serum levels of E2, P, and AMH, as well as contents of estrogen receptor (ER), progestogen receptor (PR), MVH, and Oct-4 mRNA significantly increased in the GSP group and the DHEA group (P < 0.05). CONCLUSION: GSP could improve expression levels of Oct-4, MVH, and Egr-1 mRNA in DOR mice and their ovarian function.