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STUDY QUESTION Does exposure to a mixture of ambient air pollutants during specific exposure periods influence clinical pregnancy rates in women undergoing IVF/ICSI-embryo transfer (ET) cycles? SUMMARY ANSWER The specific exposure period from ET to the serum hCG test was identified as a critical exposure window as exposure to sulfur dioxide (SO2) or a combination of air pollutants was associated with a decreased likelihood of clinical pregnancy. WHAT IS KNOWN ALREADY Exposure to a single pollutant may impact pregnancy outcomes in women undergoing ART. However, in daily life, individuals often encounter mixed pollution, and limited research exists on the effects of mixed air pollutants and the specific exposure periods. STUDY DESIGN, SIZE, DURATION This retrospective cohort study involved infertile patients who underwent their initial IVF/ICSI-ET cycle at an assisted reproduction center between January 2020 and January 2023. Exclusions were applied for patients meeting specific criteria, such as no fresh ET, incomplete clinical and address information, residency outside the 17 cities in the Sichuan Basin, age over 45 years, use of donor semen, thin endometrium (<8 mm) and infertility factors unrelated to tubal or ovulation issues. In total, 5208 individuals were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Daily average levels of six air pollutants (fine particulate matter (PM2.5), inhalable particulate matter (PM10), SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3)) were acquired from air quality monitoring stations. The cumulative average levels of various pollutants were determined using the inverse distance weighting (IDW) method across four distinct exposure periods (Period 1: 90 days before oocyte retrieval; Period 2: oocyte retrieval to ET; Period 3: ET to serum hCG test; Period 4: 90 days before oocyte retrieval to serum hCG test). Single-pollutant logistic regression, two-pollutant logistic regression, Quantile g-computation (QG-C) regression, and Bayesian kernel machine regression (BKMR) were employed to evaluate the influence of pollutants on clinical pregnancy rates. Stratified analyses were executed to discern potentially vulnerable populations. MAIN RESULTS AND THE ROLE OF CHANCE The clinical pregnancy rate for participants during the study period was 54.53%. Single-pollutant logistic models indicated that for PM2.5 during specific exposure Period 1 (adjusted odds ratio [aOR] = 0.83, 95% CI: 0.70–0.99) and specific exposure Period 4 (aOR = 0.83, 95% CI: 0.69–0.98), and SO2 in specific exposure Period 3 (aOR = 0.92, 95% CI: 0.86–0.99), each interquartile range (IQR) increment exhibited an association with a decreased probability of clinical pregnancy. Consistent results were observed with dual air pollution models. In the multi-pollution analysis, QG-C indicated a 12% reduction in clinical pregnancy rates per IQR increment of mixed pollutants during specific exposure Period 3 (aOR = 0.89, 95% CI: 0.79–0.99). Among these pollutants, SO2 (33.40%) and NO2 (33.40%) contributed the most to the negative effects. The results from BKMR and QG-C were consistent. Stratified analysis revealed increased susceptibility to ambient air pollution among individuals who underwent transfer of two embryos, those with BMI ≥ 24 kg/m2 and those under 35 years old. LIMITATIONS, REASONS FOR CAUTION Caution was advised in interpreting the results due to the retrospective nature of the study, which was prone to selection bias from non-random sampling. Smoking and alcohol, known confounding factors in IVF/ICSI-ET, were not accounted for. Only successful cycles that reached the hCG test were included, excluding a few patients who did not reach the ET stage. While IDW was used to estimate pollutant concentrations at residential addresses, data on participants' work locations and activity patterns were not collected, potentially affecting the accuracy of exposure prediction. WIDER IMPLICATIONS OF THE FINDINGS Exposure to a mixture of pollutants, spanning from ET to the serum hCG test (Period 3), appeared to be correlated with a diminished probability of achieving clinical pregnancy. This association suggested a potential impact of mixed pollutants on the interaction between embryos and the endometrium, as well as embryo implantation during this critical stage, potentially contributing to clinical pregnancy failure. This underscored the importance of providing women undergoing ART with comprehensive information to comprehend the potential environmental influences and motivating them to adopt suitable protective measures when feasible, thereby mitigating potential adverse effects of contaminants on reproductive health. STUDY FUNDING/COMPETING INTEREST(S) This work received support from the National Key Research and Development Program of China (No. 2023YFC2705900), the National Natural Science Foundation of China (Nos. 82171664, 81971391, 82171668), the Natural Science Foundation of Chongqing Municipality of China (Nos. CSTB2022NSCQ-LZX0062, CSTB2023TIAD-KPX0052) and the Foundation of State Key Laboratory of Ultrasound in Medicine and Engineering (No. 2021KFKT013). The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATERIALS, SETTING, METHODS The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

The Changlingzi Pb-Zn deposit is located in the southern Great Xing'an Range metallogenic belt of Northeast China. This deposit experienced two types of mineralization including skarn (ore block I) and hydrothermal vein (ore block II), and their orebodies are hosted mainly in the Lower Permian Zhesi Formation. The hydrothermal mineralization is classified into two metallogenic periods: skarn (stage 1) and sulfide (stages 2, 3, and 4). The skarn period affected only the ore block I, whereas the sulfide period similarly affected the two ore blocks. Fluid inclusion studies indicate that the ore-forming fluids during the early stage were medium- to high-temperature, high-salinity heterogeneous NaCl-[H.sub.2]O fluids, and that they eventually evolved to low-temperature, low-salinity homogeneous NaCl-[H.sub.2]O fluids by late stage. Studies of the hydrogen and oxygen isotope compositions ([[delta].sup.18][O.sub.H2O] = -13.85[per thousand] to 3.95[per thousand], [delta][D.sub.H2O] = -132.8[per thousand] to -102.7[per thousand]) show that the ore-forming fluids gradually evolved from magmatic water to meteoric water. Sulfur and lead date suggest that the ore-forming materials were probably derived from deep magma and the Permian strata. Although our data show that ore blocks I and II, in terms of genesis, were skarn- and medium-to low-temperature hydrothermal vein-types, respectively, the ore-forming fluids of both ore blocks were the same period, and the differences in mineralization type can be related to the wall rocks.Le gisement de Pb-Zn de Changlingzi est situe dans la partie meridionale de la ceinture metallogenique de la chaine du Grand Khingan du nord-est de la Chine. Le gisement a connu deux types de mineralisation, dont une skarnification (bloc mineralise I) et la formation de filons hydrothermaux (bloc mineralise II), les corps mineralises associes se trouvant principalement dans la Formation de Zhesi du Permien inferieur. La mineralisation hydrothermale est sous-divisee en deux periodes metallogeniques, a skarn (stade 1) et a sulfures (stades 2, 3 et 4). La periode de skarnification ne se manifeste que dans le bloc mineralise I. La periode de mineralisation en sulfures presente des elements semblables dans les deux blocs mineralises. L'etude des inclusions fluides indique que les fluides mineralisateurs durant le premier stade etaient des fluides heterogenes riches en NaCl-[H.sub.2]O de temperature moyenne a elevee et de forte salinite, qui ont fait place a des fluides homogenes riches en NaCl-[H.sub.2]O de faibles temperature et salinite aux stades de mineralisation plus tardifs. L'etude de la composition des isotopes d'hydrogene et d'oxygene ([[delta].sup.18][O.sub.H2O] = -13,85 [per thousand] a 3,95 [per thousand], [delta][D.sub.H2O] = -132,8 [per thousand] a -102,7 [per thousand]) montre que la source des fluides mineralisateurs est graduellement passee d'eau magmatique a de l'eau meteorique. Les donnees d'isotopes de soufre et de plomb indiqueraient que les materiaux mineralisateurs etaient probablement derives de magma profond et des strates permiennes. Si nos donnees montrent que, du point de vue de leur formation, les blocs mineralises I et II etaient, respectivement, de types skarn et filons hydrothermaux de temperature moyenne a faible, les fluides mineralisateurs des deux blocs etaient contemporains, et les differents types de mineralisation peuvent etre relies a la nature des roches encaissantes. [Traduit par la Redaction], IntroductionThe southern Great Xing'an Range (SGXR) is an important metallogenic belt in northeastern China (Liu et al. 2004; Wang et al. 2001; Zeng et al. 2011). Since the late Paleozoic, [...]

Most skarns are found near the pluton or in lithologies containing at least some limestone. However, recent research has shown that neither a pluton nor limestone is necessarily required to form a skarn deposit. The newly discovered Bagenheigeqier Pb–Zn skarn deposit is located in NE China. The skarn and Pb–Zn orebodies occur in volcanic lithologies of the Baiyin'gaolao Formation and are controlled by NE–SW-trending faults. The nearest pluton is a granite porphyry, at a distance of 20–250 m from the orebodies. Five paragenetic stages at Bagenheigeqier are recognized: (I) skarn; (II) oxide; (III) early sulphide; (IV) late sulphide; and (V) late quartz–calcite. The fluid inclusions from stages II to V homogenized at temperatures of 402–452, 360–408, 274–319 and 167–212°C, respectively. The hydrogen and oxygen isotope compositions (δ18OH2O, –12.4‰ to +9.3‰; δDH2O, –156.5‰ to –99.1‰) indicate that the ore-fluids were primarily of magmatic origin, with the proportion of meteoric water increasing during the progression of ore formation. Sulphur isotope values (δ34SVCDT, 1.4–5.5‰), lead isotope values (206Pb/204Pb, 18.184–18.717; 207Pb/204Pb, 15.520–15.875; 208Pb/204Pb, 37.991–38.379) and the initial 187Os/188Os ratios of the pyrite (0.307 ± 0.06) suggest that the ore metals were derived from the granite porphyry and Baiyin'gaolao Formation. Re–Os dating of pyrite intergrown with galena and sphalerite yielded a well-constrained isochron age of 151.2 ± 4.7 Ma, which is coeval with the laser ablation – inductively coupled plasma – mass spectrometry zircon U–Pb age of 154 ± 1 Ma for the granite porphyry. The deposit was therefore formed during Late Jurassic time. [ABSTRACT FROM AUTHOR]

New, high-sensitivity and high-resolution spectroscopic and imaging methods may be developed by exploiting nuclear magneto-optic effects. A first-principles electronic structure formulation of nuclear electric quadrupole moment-induced Cotton-Mouton effect (NQCME) is presented for closed-shell atoms. In NQCME, aligned quadrupole moments alter the index of refraction of the medium along with and perpendicular to the direction of nuclear alignment. The roles of basis-set convergence, electron correlation, and relativistic effects are investigated for three quadrupolar noble gas isotopes: 21Ne, 83Kr, and 131Xe. The magnitude of the resulting ellipticities is predicted to be 10-4-10-6 rad/(M cm) for fully spin-polarized nuclei. These should be detectable in the Voigt setup. Particularly interesting is the case of 131Xe, in which a high degree of spin polarization can be achieved via spin-exchange optical hyperpolarization. [ABSTRACT FROM AUTHOR]

In nuclear magneto-optic spectroscopy, effects of nuclear magnetization are detected in light passing through a sample containing spin-polarized nuclei. An optical analogue of nuclear magnetic resonance (NMR) chemical shift has been predicted and observed in the nuclear spin optical rotation of linearly polarized light propagating parallel to the nuclear magnetization. A recently proposed magneto-optic analogue of the NMR spin-spin coupling, the nuclear spin-induced Cotton-Mouton (NSCM) effect entails an ellipticity induced to linearly polarized light when passing through a medium with the nuclear spins polarized in a direction perpendicular to the light beam. Here we present a first-principles electronic structure formulation of NSCM in terms of response theory as well as ab initio and density-functional theory calculations for small molecules. The roles of basis set (we use completeness-optimized sets), electron correlation, and relativistic effects are discussed. It is found that the explicitly temperature-dependent contribution to NSCM, arising from the partial orientation of the molecules due to the nuclear magnetization, typically dominates the effect. This part of NSCM is proportional to the tensor product of molecular polarizability and the NMR direct dipolar coupling tensor. Hence, NSCM provides a means of investigating the dipolar coupling and, thus, molecular structure in a formally isotropic medium. Overall ellipticities of the order of magnitude of 10-8...10-7 rad/(M cm) are predicted for fully polarized nuclei. These should be detectable with modern instrumentation in the Voigt setup. [ABSTRACT FROM AUTHOR]

Introduction: Stomatin-like protein 2 (SLP2) is highly expressed in human first trimester trophoblast cells, but its functions in placental morpho-physiology remain unknown. This study aimed to determine the role of SLP2 in the proliferation and invasion of human first trimester trophoblast cells.Methods: Immunofluorescence was used to determine the expression and localization of SLP2 in normal and miscarriage human first trimester placenta. Western blot was used to determine the expression of SLP2, PCNA, Cyclin D3, N-cadherin, Vimentin, PGC1α and PPARα in HTR-8/SVneo cells. SLP2 was knocked down in the HTR-8/SVneo cells by using si-Slp2. Wound healing and migration assays were used to determine the effect of SLP2 knockdown on the migration and invasion in the HTR-8/SVneo cells. Mitochondrial membrane potential, reactive oxygen species (ROS), ATP production and biogenesis were measured to assess the effects of SLP2 knockdown on mitochondrial functions.Result: SLP2 was strongly expressed in the cytotrophoblasts (CTB), syncytiotrophoblast (STB) and extravillous trophoblasts (EVT) of normal pregnancy placenta as compared to miscarriage placenta. SLP2 was highly expressed in the invasive EVT cell lines, HTR-8/SVneo and HPT-8 compared to the CTB cell line JAR. Knockdown of SLP2 significantly inhibited the migration and invasion of HTR-8/SVneo cells and placental villous explants, and repressed mitochondrial biogenesis and functions in HTR-8/SVneo cells.Discussion: Silencing of SLP2 inhibited the proliferation, migration and invasion of HTR-8/SVneo cells via the impairment of mitochondrial functions. This indicates that the downregulation of SLP2 in miscarriage placenta could be part of the pathogenesis and pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

New LA–ICP–MS zircon U–Pb geochronology, whole‐rock major and trace element geochemistry data, and petrographic observations are presented for three granitic dykes in the Changlingzi area of NE China. These data provide precise age and petrogenesis information with respect to the late Palaeozoic–Mesozoic intrusions in the area, which further constrain the geodynamic evolution of the southern Great Xing'an Range. Our zircon U–Pb data denote that the felsic dykes were emplaced during the Late Permian (~254 Ma) and Late Jurassic (143–142 Ma). Geochemically, the Late Permian monzonite porphyries are characterized by high Al2O3 (16.52–16.92 wt%) and Sr (490–579 ppm) contents and low Yb (0.52–0.57 ppm), Y (5.7–6.3 ppm), and heavy rare earth element (HREE) contents, which indicate an adakitic affinity. The Late Jurassic felsic dykes are characterized by high FeOt/MgO (8.2–11.9) and Ga/Al (3.3–3.8) ratios, high zircon saturation temperatures (888–929°C), and remarkable negative Eu (Eu/Eu* = 0.25–0.42) anomalies, indicating they are akin to A‐type granites. The Late Permian adakitic magma resulted from the partial melting of thickened lower crust, and was formed during collisional orogenesis related to subduction of Palaeo‐Asian Ocean crust. The Late Jurassic A‐type magmas were probably generated by the partial melting of amphibolite‐facies lower crustal materials. The melting occurred in response to the upwelling of asthenospheric material caused by collapse of thickened crust, due to gravitational instability during closure of the Mongol–Okhotsk Ocean. Subsequently, the latest stage of magmatic activity in this area and elsewhere in NE China was controlled mainly by subduction of Palaeo‐Pacific Ocean crust. [ABSTRACT FROM AUTHOR]

The recently discovered Bulage Pb–Zn deposit is located in the central part of the Erlianhot–Dongwuqi Metallogenic Belt (eastern Central Asian Orogenic Belt) in Inner Mongolia, China. The ore bodies of the deposit are hosted in alkali feldspar granite and in dacitic crystal tuff within Unit 2 of the Carboniferous Baoligaomiao Formation. The Bulage deposit is a low to moderate temperature hydrothermal vein‐type deposit and is controlled by fractures. The hydrothermal mineralization can be divided into three stages: early (quartz + specularite ± magnetite), middle (quartz + sphalerite + galena ± chalcopyrite ± pyrite), and late (calcite ± quartz + sphalerite + galena). The deposit contains liquid‐rich two‐phase (VL‐type) and pure‐liquid (L‐type) fluid inclusions. The initial ore‐forming fluids are attributed to the low to moderate temperature and low salinity of a NaCl–H2O system. Hydrogen and oxygen isotopic compositions of quartz and calcite indicate that the ore‐forming fluids were dominated by meteoric water with minor contributions of magmatic water. The quartz diorite, monzonite porphyry, and alkali feldspar granite in the deposit yield LA–ICP–MS zircon U–Pb ages of 305–300 Ma. These high‐K calc‐alkaline I‐type granitoids are enriched in large‐ion lithophile elements (LILEs; e.g., Rb, Cs, and K) and light rare earth elements (LREEs) and are depleted in high‐field‐strength elements (HFSEs; e.g., Nb, Ta, and Ti) and heavy rare earth elements (HREEs). The primary magma of these granitoids was derived from the partial melting of lower crust. The parental magma of the quartz diorite may have provided part of the ore‐forming material and acted as a heat source for mineralization. Therefore, we infer that the Bulage Pb–Zn deposit was formed as a result of the southward subduction of the Paleo–Asian Ocean beneath the North China Craton during the Late Carboniferous. [ABSTRACT FROM AUTHOR]

Study Question: Does nm23 have functional significance in decidualization in mice and humans?Summary Answer: nm23 affects decidualization via the phosphoinositide 3 kinase/mammalian target of rapamycin (PI3K-Akt-mTOR) signaling pathways in mouse endometrial stromal cells (ESCs; mESCs) and human ESCs.What Is Known Already: The function of nm23 in suppressing metastasis has been demonstrated in a variety of cancer types. nm23 also participates in the control of DNA replication and cell proliferation and differentiation.Study Design, Size and Duration: We first analyzed the expression profile of nm23 in mice during early pregnancy (n = 6/group), pseudopregnancy (n = 6/group) and artificial decidualization (n = 6/group) and in humans during the menstrual cycle phases and the first trimester. We then used primary cultured mESCs and a human ESC line, T-HESC, to explore the hormonal regulation of nm23 and the roles of nm23 in in vitro decidualization, and as a possible mediator of downstream PI3K-Akt-mTOR signaling pathways.Participants/materials, Settings and Methods: We evaluated the dynamic expression of nm23 in mice and humans using immunohistochemistry, western blot and real-time quantitative RT-PCR (RT-qPCR). Regulation of nm23 by steroid hormones was investigated in isolated primary mESCs and T-HESCs by western blot. The effect of nm23 knockdown (using siRNA) on ESC proliferation was analyzed by 5-ethynyl-2'-deoxyuridine staining (EdU) and proliferating cell nuclear antigen protein (PCNA) expression. The influence of nm23 expression on the differentiation of ESCs was determined by RT-qPCR using the mouse differentiation markers decidual/trophoblast PRL-related protein (dtprp, also named prl8a2) and prolactin family 3 subfamily c member 1 (prl3c1) and the human differentiation markers insulin-like growth factor binding protein 1 (IGFBP1) and prolactin (PRL). The effects of nm23 siRNA (si-nm23) and the PI3K inhibitor LY294002 on the downstream effects of nm23 on the PI3K-Akt-mTOR signaling pathway were estimated by western blot.Main Results and the Role Of Chance: NM23-M1 was specifically expressed in the decidual zone during early pregnancy and in artificially induced deciduoma, and NM23-H1 was strongly expressed in human first trimester decidua. The expression of nm23 was upregulated by oestradiol and progesterone (P < 0.05 versus control) in vitro in mESCs and T-HESC, and this was inhibited by their respective receptor antagonists, ICI 182,780 and RU486. Mouse and human nm23 knockdown decreased ESC proliferation and differentiation (P < 0.05 versus control). The PI3K-Akt-mTOR signaling pathways were downstream mediators of nm23 in mESCs and T-HESCs decidualization.Limitations and Reasons For Caution: Whether the nm23 regulates decidualization via the activation of AMPK, RAS, PKA, STAT3 or other signaling molecules remains to be determined. The role of nm23 in decidualization was tested in vitro only.Wider Implications Of the Findings: Results demonstrate that nm23 plays a vital role in decidualization in mice and humans and that nm23 gene expression is hormonally regulated. The downregulation of nm23 in decidua during the first trimester may be associated with infertility in women.Study Funding/competing Interests: This study was supported by the National Natural Science Foundation of China (grant nos. 81370731, 31571551 and 31571190), the Science and Technology Project of Chongqing Education Committee (KJ130309), open funding by the Chongqing Institute for Family Planning (1201) and the Excellent Young Scholars of Chongqing Medical University (CQYQ201302). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Organic cation/carnitine transporter 2 (OCTN2) is responsible for the cellular uptake of the antineoplastic agent, oxaliplatin. Epigenetic modification is a possible mechanism of altered drug-transporter expression in cancers, leading to altered efficacy of chemotherapeutic drugs. However, the mechanisms governing OCTN2 regulation are not completely understood. In this study, the low levels of OCTN2 in HepG2 and LS174T cells were elevated by the demethylating reagent, decitabine (DCA). To further reveal the epigenetic mechanism of down-regulation of OCTN2, we found that Region-1 within the OCTN2 promoter (spanning −354 to +85) was a determinant of OCTN2 expression in a luciferase reporter assay. Moreover, methylation-specific PCR (MSP) and bisulfite genomic sequencing showed that the degree of individual methylated CpG sites within this region was inversely correlated with the levels of OCTN2 in different cancer cells. Application of DCA to HepG2 and LS174T cells reversed the hypermethylation status of the OCTN2 promoter and increased OCTN2 expression, enhancing cellular uptake of oxaliplatin. Thus, we identified that promoter methylation is responsible for epigenetic down-regulation of OCTN2 in HepG2 and LS174T cells. Given the essential role of OCTN2 in cancer cell uptake of chemotherapeutics, and thus treatment efficacy, pretreatment with a demethylating reagent is a possible strategy for optimizing pharmacotherapies against cancers. [ABSTRACT FROM AUTHOR]

Ever since the first attempt at its synthesis in 1912, cyanogen azide (NCN3) has continued to attract the attention of chemists in diverse fields such as photochemistry, organic chemistry, and energetic materials. However, to our great surprise, its isocyanide isomer, CNN3, has not been studied experimentally or theoretically. In this paper, for the first time, we report a theoretical spectroscopic and stability study of CNN3 employing the CCSD and CCSD(T) methods with the aug-cc-pVTZ basis set. In light of its potential multi-reference character, the isomers and transition state structures on the reaction pathway were re-optimized using the multi-configurational CASSCF method in conjunction with the cc-pVTZ basis set. It is shown that CNN3 should be intrinsically stable both with respect to isomerization and fragmentation. The structural and spectroscopic properties obtained in this study should provide useful information for the future laboratory identification of CNN3. For comparison, we also calculated the aug-cc-pVTZ-CCSD(T) and cc-pVTZ-CASSCF properties of NCN3. [ABSTRACT FROM AUTHOR]

Recently, a combined laser ablation and density functional theory study (Jiang and Xu, J. Am. Chem. Soc. 2005, 127, 8906) claimed the existence of the long-sought 18-electron member of the first-row transition metal carbonyl complex, Zn(CO)3. In this paper, we systematically investigate the thermodynamic and kinetic stability of Zn(CO)3towards CO-extrusion at the BP86, B3PW91, BPW91, PBEPBE, BH&HLYP, B3LYP, MP2, MP4SDQ, QCISD, CCSD and CASPT2 levels as well as the Born–Oppenheimer molecular dynamic (BOMD) simulation. All these calculations consistently reveal that the 18e Zn(0) complex Zn(CO)3is neither a genuine minimum point nor kinetically stable with negligibly low barriers. In particular, Zn(CO)3is quite thermodynamically unstable with respect to the fragments 1Zn + 3CO by around 40 kcal mol−1at all the three sophisticated correlation levels, i.e., MP4SDQ, QCISD and CCSD. We thus conclude that the tricarbonyl Zn(0) complex, Zn(CO)3, should not exist even for spectroscopic characterization. Interestingly, our extensive structural search predicts that two triplet di-zinc carbonyls, i.e., 3(CO)ZnZn and 3(CO)2ZnZn, have noticeable kinetic stability (10.41 and 8.11 kcal mol−1at the CCSD level) against the respective CO- and Zn-extrusion, which can be compared with the value 8.70 kcal mol−1for the already detected 3Zn(CO)2(Jiang and Xu, J. Phys. Chem. A2006,110, 7092). Our designed 3(CO)ZnZn and 3(CO)2ZnZn together with the experimentally known 3ZnCO and 3Zn(CO)2are formally associated with the zinc (0) “spin-based zinc carbonyls” and should be considered as remarkable, since most of the known zinc complexes usually contain +2 or +1 oxidation state Zn. [ABSTRACT FROM AUTHOR]

In this work, we report the first comparative study directly between AI[subn]H[subn+2] and B[subn]H[subn+2] (5 ⩽ n ⩽ 12), Al[subn]H[subn+2] and B[subn]H[subn+2] (4 ⩽ n ⩽ 12) covering diverse structural forms. It was shown that AI[subn]H[subn+2] each have a closo ground structure as B[subn]H[sub+2], nicely consistent with the Wade-Mingos rule. However, Al[subn]H[subn+2] adopt the closo-nido ground structures following the even-odd alternation in the number of Al atoms, showing `distinct violation of the Wade-Mingos rule for the odd-numbered Al-atoms. Interestingly, the corresponding B[subH][subn+2] also have similar closo (even)-nido (odd) alternation. Therefore, our direct comparison showed that AI[subn]H[subn+2] (5 ⩽ n ⩽ 12) and Al[subn]H[subn+2] (4 ⩽ n ⩽12) can be viewed as the borane analogues, though not all AI[subn]H[subn+2] have the ability of being explained by Wade-Mingos rule. So, the analogy between alanes and boranes in form of X[subn]H[subn+]2 should not be simply judged by the Wade-Mingos rule because of the significant influence of the additional two hydrogen atoms on the closo-structure. [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate the prevalence of occult hepatitis B virus (HBV) infection among hepatopathy patients and healthy people in China. Methods: The HBV DNA in 653 sera samples collected from cryptogenic chronic liver disease patients (159), hepatitis B surface antigen (HBsAg) negative hepatocellular carcinoma (HCC) patients (135) and HBsAg-negative healthy people (359) were tested by nested PCR using specific primers of the X region of the HBV genome. We performed real-time PCR to determine the levels of serum HBV–DNA. Results: Prevalence of occult HBV infection was 28.3% (45/159), 70.4% (95/135) and 10.6% (38/359) in cryptogenic chronic liver disease patients, HBsAg-negative HCC patients and HBsAg-negative healthy people, respectively. The prevalence of occult HBV infection in IgG anti-HBc-positive subjects was 100% (45/45), 86.7% (85/98) and 33.3% (14/42) in cryptogenic chronic liver disease patients, HBsAg-negative HCC patients and HBsAg-negative healthy people, respectively. In all cases, viral loads were low (<104 viral copies/mL). Conclusion: The prevalence of occult HBV infection was significantly high among hepatopathy patients and healthy people in China. Thus, more meticulous attention should be given to prevent HBV transmission by blood transfusion or organ transplantation in endemic areas, and further studies on clinical implication and mechanism of occult HBV infection are required. [Copyright &y& Elsevier]

Objective: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth., Methods: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role., Results: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes., Conclusions: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)