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In brief The current declining trend in male fertility parallels the increasing prevalence of obesity worldwide. This paper revealed that the poor in vitro fertilization rates and decreased sperm motility in obese mice due to excessive oxidative stress enhanced apoptosis and impaired glucose metabolism in the testes. Abstract Obesity is an urgent public health problem in recent decades, linked to reduced reproductive potential, and negatively affects the success of assisted reproduction technology. The aim of this study is to investigate the mechanisms underlying impaired male fertility caused by obesity. Male C57BL/6 mice fed a high-fat diet for 20 weeks served as mouse models with moderate (20% < body fat rate (BFR) < 30%) and severe obesity (BFR > 30%). Our results showed poor in vitro fertilization rates and decreased sperm motility in obese mice. Abnormal testicular structures were identified in male mice with moderate and severe obesity. The expression level of malondialdehyde increased with obesity severity. This finding indicates that oxidative stress plays a role in male infertility caused by obesity, which was further confirmed by the decreased expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase, and glutathione peroxidases. Our study also found that the expression of cleaved caspase-3 and B-cell lymphoma-2 showed an obesity severity-dependent manner indicating that apoptosis is highly correlated with male infertility caused by obesity. Moreover, the expression of glycolysis-related proteins, including glucose transporter 8, lactate dehydrogenase A, monocarboxylate transporter 2 (MCT2), and MCT4, decreased significantly in the testes of obese male mice, suggesting energy supply for spermatogenesis is impaired by obesity. Taken together, our findings provide evidence that obesity impairs male fertility through oxidative stress, apoptosis, and blockage of energy supply in the testes and suggest that male obesity influences fertility through complex and multiple mechanisms.

CRISPR/Cas9-mediated site-specific insertion of exogenous genes holds potential for clinical applications. However, it is still infeasible because homologous recombination (HR) is inefficient, especially for non-dividing cells. To overcome the challenge, we report that a homology-independent targeted integration (HITI) strategy is used for permanent integration of high-specificity-activity Factor IX variant (F9 Padua, R338L) at the albumin (Alb) locus in a novel hemophilia B (HB) rat model. The knock-in efficiency reaches 3.66%, as determined by droplet digital PCR (ddPCR). The clotting time is reduced to a normal level four weeks after treatment, and the circulating factor IX (FIX) level is gradually increased up to 52% of the normal level over nine months even after partial hepatectomy, demonstrating the amelioration of hemophilia. Through primer-extension-mediated sequencing (PEM-seq), no significant off-target effect is detected. This study not only provides a novel model for HB but also identifies a promising therapeutic approach for rare inherited diseases.

Alternating conditions from cold to warm periods since the Late Glacial provided a significant contrast for future hydroclimatic variation, as did the corresponding variation in vegetation. To predict the potential variability in C3/C4 biomass under future warmer climatic conditions, we determined the current spatiotemporal distribution of C3 and C4 vegetation by estimating the variability of δ13Corg values in 125 topsoil samples and investigating the geological period variability of C4 plants growing in Inner Mongolia, China. We examined the factors contributing to the growth of C4 plants and the variability in C4 plants for each 1 °C increase in temperature during recent and geological times. The results revealed that the relative abundance of C4 plants in Inner Mongolia shows an increasing trend from the northwest to the southeast. The biomass of C4 plants was found to be positively correlated with temperature, although weakly correlated with precipitation, thereby indicating that temperature is the primary climatic factor determining the growth of C4 plants in this region. Furthermore, we found that in response to each 1 °C increase in temperature, there would be an approximate 2.1% increase in the spatiotemporal variation of present-day C4 plant biomass in Inner Mongolia, whereas during the geological period, there was a corresponding increase of 10.7%. Comparatively, the spatiotemporal variation in present-day C4 biomass on the Chinese Loess Plateau has undergone a 4.0% increase in response to each 1 °C increase in temperature, whereas 6.0% and 7.5% increases in the geological period were estimated based on core samples taken from the Lantian and Xingyang sections, respectively. Interestingly, for each 1 °C increase in temperature during the current growth month of C4 plants, there is a 6.6% increase in C4 biomass, which is essentially consistent with the results obtained for the geological period results (i.e., 6.0% and 7.5% for the Lantian and Xingyang sections, respectively). The findings of this study reveal a distinct contrast in the variation of C4 plants during recent and geological periods, thereby enabling us to quantitatively estimate the potential changes in C4 vegetation in response to projected climate conditions.

The organic-rich shale of the Upper Carboniferous-Lower Permian transition period in the eastern margin of the Ordos Basin, China, was formed in a marine-continental facies sedimentary environment. With a high content of total organic carbon (TOC) and a large cumulative thickness, it is considered a good source rock for shale gas development. The sedimentary environment of marine-continental transitional shale is obviously different from that of marine shale, which leads to different enrichment characteristics of organic matter. In this paper, shale samples were collected from XX# well of the Taiyuan and Shanxi Formations across the Upper Carboniferous-Lower Permian, which is typical marine-continental transitional shale. The TOC, major elements, and trace elements were measured, and the formation and preservation conditions were investigated using multiple geochemical proxies, including paleoclimate, redox parameters, paleoproductivity, and controls on the accumulation of organic matter. The TOC of Shanxi Formation is higher than that of Taiyuan Formation. In the Taiyuan Formation, TOC is positively related to the redox index (V, U, and V/Cr), indicating that the dysoxic bottom water environment is the key factor controlling organic matter accumulation. For Shanxi Formation, there is a positive correlation between TOC and paleoclimate, which indicates that the enrichment of organic matter is affected by warm and humid paleoclimate and oxic environment. In addition, the paleoproductivity is lower with a positive correlation with TOC for the marine-continental transitional organic-rich shale, suggesting that it was inferior to the gathering of organic matter.

Black shale deposited in the transitional period from the Late Ordovician to Early Silurian is the most important source rock and shale gas reservoir in the Yangtze region of South China. However, the source of these sediments is still controversial. In this paper, the changes in total organic carbon (TOC), total sulfur (TS), organic carbon isotopes (δ13Corg), biomarkers, trace elements, and rare earth elements in the Ordovician–Silurian boundary strata of the XK-1 well in northern Guizhou Province, South China, have been systematically studied. The paleoenvironmental and paleoclimatic conditions of the Late Ordovician to Early Silurian and their relationship with organic matter enrichment in the Upper Yangtze Platform have been reconstructed. The distribution of biomarkers reflects that the Late Ordovician–Early Silurian shale was deposited in the marine environment and was highly contributed by marine plankton/algae and microorganisms. Paleoclimatic proxies (Sr/Cu, δ13Corg) show that the global climate system experienced significant changes from a warm-humid climate to a brief period of cold-dry climate and then back to a warm-humid climate during the Ordovician–Silurian transition. This warm and humid climate condition helps to improve the biological productivity within the photic zone of the water column during deposition. In addition, the low oxygen (reduction) conditions during the deposition of the Late Ordovician–Early Silurian deposits are characterized by low Pr/Ph values (0.39–0.79) and relatively high elemental ratios of V/Ni (1.40–5.77) and V/(V + Ni) (0.58–0.85). This paleoredox condition contributes to the preservation of organic matter during deposition of the Late Ordovician–Early Silurian deposits. Therefore, it is demonstrated that the climate and ocean fluctuated greatly during the Late Ordovician–Early Silurian transition period, and this fluctuation provided necessary control factors for marine anoxia, primary productivity, and subsequent organic-rich black shale deposition in the Upper Yangtze region during the Late Ordovician and Early Silurian intervals.

Base editing technology efficiently generates nucleotide conversions without inducing excessive double-strand breaks (DSBs), which makes it a promising approach for genetic disease therapy. In this study, we generated a novel hereditary tyrosinemia type 1 (HT1) mouse model, which contains a start codon mutation in the fumarylacetoacetate hydrolase (Fah) gene by using an adenine base editor (ABE7.10). To investigate the feasibility of base editing for recombinant adeno-associated virus (rAAV)-mediated gene therapy, an intein-split cytosine base editor (BE4max) was developed. BE4max efficiently induced C-to-T conversion and restored the start codon to ameliorate HT1 in mice, but an undesired bystander mutation abolished the effect of on-target editing. To solve this problem, an upstream sequence was targeted to generate a de novo in-frame start codon to initiate the translation of FAH. After treatment, almost all C-to-T conversions created a start codon and restored Fah expression, which efficiently ameliorated the disease without inducing off-target mutations. Our study demonstrated that base editing-mediated creation of de novo functional elements would be an applicable new strategy for genetic disease therapy.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and it lacks an efficient target treatment. Here, we aimed to gain knowledge on the development of TNBC research and explore potential treatment strategies.Methods: We analyzed 14,389 publications on TNBC from the Web of Science (WOS) over the past 20 years, from 2000 to 2020, using bibliometric methods. We evaluated the publication tendency of TNBC and the contributions of different countries. Institutions and journals with the highest number of TNBC publications were screened. Finally, the research focus of the TNBC publications were also analyzed.Results: TNBC publications have significantly increased in the past 20 years, with elevated relative research interest (RRI). The USA has the most TNBC-related publications with high quality, and China is the country with the most rapid growth tendency in TNBC publications. The University of Texas System is the institution with the most TNBC publications. Breast Cancer Research and Treatment is the journal that published the most TNBC-related publications. The top 30 publications with high citations are also listed. The researches focusing on TNBC in the past 20 years were separated into four main clusters: tumor biology, TNBC therapies, treatment sensitivity, and gene mutations. The research focus in TNBC ranked by appearing years reflects the development of TNBC treatment strategy, showing that targeting tumor immunity is now the main focus in TNBC research. Conclusions: Using bibliometric analysis, we initially revealed the increasing interest in TNBC research and summarized the publication tendency of TNBC. We also reported focused topics screened from publications in the past 20 years, indicating the main problems and research objectives of TNBC for the first time. Immune-related topics are becoming the focus of TNBC research.

Multi-proxy records of paleoclimate changes spanning the past 30 cal ka BP were obtained from Qionghai Lake sediment core, Sichuan Province, southwest China, where southwest summer monsoon prevails. The core was studied for molecular compositions of n-alkanes, stable carbon isotope ratios (δ13C) of organic matter (OM), total organic carbon (TOC), total nitrogen (TN) and trace elements. Evidence from n-alkanes, cross chart of C/N-δ13C values and trace elements indicated the organic matter derived from a mixed source composed of autochthonous aquatic organisms and allochthonous terrestrial plants, and the sediments mainly deposited in reducing conditions, which is in favor of preservation and accumulation of OM. Variations of n-alkanes biomarker proxies, δ13C of organic matter and Mo concentrations reflected three stages of paleoclimate evolution during the past 30 cal ka BP: a relatively warm and humid climate between 29.1 and 22.9 cal ka BP, corresponding to a strong southwest summer monsoon; climate shifted towards cold and dry condition during the period of 22.9–15.7 cal ka BP, in response to the reduced insolation and weakened southwest summer monsoon; temperature and humidity gradually increased in the Holocene with fluctuations, broadly track the strengthening trend of southwest summer monsoon. Our findings further confirm that variations in solar activity may primarily affect the strength of southwest summer monsoon, resulting in the shifts of paleoclimate conditions. Further studies are needed to better constrain the detailed forcing drivers which may amplify the intensity of southwest summer monsoon particularly in the Holocene period.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) technology is widely used as a tool for gene editing in rat genome site-specific engineering. Multidrug resistance 1 [MDR1 (also known as P-glycoprotein)] is a key efflux transporter that plays an important role not only in the transport of endogenous and exogenous substances, but also in tumor MDR. In this report, a novel MDR1 (Mdr1a/b) double-knockout (KO) rat model was generated by the CRISPR/Cas9 system without any off-target effect detected. Western blot results showed that MDR1 was completely absent in the liver, small intestine, brain, and kidney of KO rats. Further pharmacokinetic studies of digoxin, a typical substrate of MDR1, confirmed the deficiency of MDR1 in vivo. To determine the possible compensatory mechanism of Mdr1a/b (-/-) rats, the mRNA levels of the CYP3A subfamily and transporter-related genes were compared in the brain, liver, kidney, and small intestine of KO and wild-type rats. In general, a new Mdr1a/b (-/-) rat model has been successfully generated and characterized. This rat model is a useful tool for studying the function of MDR1 in drug absorption, tumor MDR, and drug target validation.

Site-specific integration of exogenous gene through genome editing is a promising strategy for gene therapy. However, homology-directed repair (HDR) only occurring in proliferating cells is inefficient especially in vivo. To investigate the efficacy of Cas9-induced homology-independent targeted integration (HITI) strategy for gene therapy, a rat hemophilia B model was generated and employed. Through HITI, a DNA sequence encoding the last exon of rat Albumin (rAlb) gene fused with a high-specific-activity Factor IX variant (R338L) using T2A, was inserted into the last intron of rAlb via recombinant adeno-associated viral (rAAV). The knock-in efficiency reached up to 3.66% determined by ddPCR. The clotting time was reduced to normal level 4 weeks after treatment, and the circulating FIX level was gradually increased up to 52% of normal during 9 months even after partial hepatectomy, demonstrating the amelioration of hemophilia. Through PEM-seq, no significant off-targeting effect was detected. Moreover, this study provides a promising therapeutic approach for hereditary diseases.

Site-specific integration of exogenous gene through genome editing is a promising strategy for gene therapy. However, homology-directed repair (HDR) only occurring in proliferating cells is inefficient especially in vivo. To investigate the efficacy of Cas9-induced homology-independent targeted integration (HITI) strategy for gene therapy, a rat hemophilia B model was generated and employed. Through HITI, a DNA sequence encoding the last exon of rat Albumin (rAlb) gene fused with a high-specific-activity Factor IX variant (R338L) using T2A, was inserted into the last intron of rAlb via recombinant adeno-associated viral (rAAV). The knock-in efficiency reached up to 3.66% determined by ddPCR. The clotting time was reduced to normal level 4 weeks after treatment, and the circulating FIX level was gradually increased up to 52% of normal during 9 months even after partial hepatectomy, demonstrating the amelioration of hemophilia. Through PEM-seq, no significant off-targeting effect was detected. Moreover, this study provides a promising therapeutic approach for hereditary diseases.

The distribution characteristics of typical heavy metals (HMs) and Pb isotopic compositions in profile soils from different areas were investigated in Baiyin district, northwest China. The soil samples from the ore district and the sewage irrigation area showed an obvious enrichment of HMs in different depths, and the difference in the longitudinal migration depth of Pb, Cu, Zn, and Cd was insignificant, which might be due to the migration behavior of HMs mainly controlled by carbonate in alkaline soil. With the sewage irrigation activities, the content of soil organic matter was no longer the main controlling factor for the migration behavior of HMs. In ore district and sewage irrigation area, the HMs contents of nonresidual fractions in topsoil were much higher than that in the corresponding deep soil, which indicated that HMs activities in topsoil were significantly high. The Pb isotopic compositions of profile soils indicated that the long-term mining and smelting activities remained the main source of vertical enrichment of HMs in Baiyin district. Moreover, the Pb isotope ratios 206Pb/207Pb of nonresidual fractions (1.1359-1.1916) were all lower than that in the corresponding residual fractions (1.1641-1.2010), showing the characteristics that HMs input from anthropogenic source were in different degrees. The Pb isotopic compositions of residual fractions in the topsoil of ore district and sewage irrigation area (1.1641 and 1.1703) were between the two end-members composed of background soil and local mineral samples, which suggested that some anthropogenic HMs might enter into the residual components in the soil that was greatly affected by the input of HMs.

Organic geochemical and trace element analysis of a suite of 33 samples collected from the Shangsi section of the Upper Permian Dalong Formation, located near Guangyuan in the northwestern Sichuan Basin, have been used to better understand the marine depositional environment of its shale lithofacies. A 15 m-thick black shale interval near the middle of the formation is enriched in total organic carbon (TOC = 1.1–14.4%, mean = 6.4%). The n-alkane, terpane and sterane biomarker distributions of the shale suggest that its organic matter is of predominantly marine algal origin. Pr/Ph, Pr/n-C17, Ph/n-C18 and gammacerane/C30 hopane ratios demonstrate that reducing conditions prevailed during its deposition. This interpretation is supported by the redox-sensitive abundance of Mo and the trace element redox ratios Ni/Co, V/Cr, U/Th and V/(V + Ni), all of which indicate deposition in a euxinic/anoxic setting. The Mo-TOC relationship in the Dalong shales plots mid-way between those of sediments in the present-day Saanich Inlet and Cariaco Basin, suggesting a moderately restricted depocentre. However, the δ13Corg values of these shales reveal that their organic matter is isotopically much lighter than that found in modern euxinic sediments, implying extremely anoxic bottom waters and a slow-down of oceanic circulation during the Late Permian.

An accurate chronological framework is vital if we are to use lacustrine sediments on the Tibetan Plateau (TP) for paleoclimate reconstruction. Radiocarbon (14C) dating is the most frequently used method for dating late Quaternary lacustrine sediments. However, it is often affected by potential reservoir effects. Owing to the complex hydrogeology and sedimentology processes of the lake we study in this paper, it is difficult to correct this effect. Geomagnetic relative paleointensity (RPI) method has demonstrated the potential to construct an accurate high-resolution chronological framework for sediments in the Brunhes chron. In this study, we present an RPI record as well as environmental magnetism results from a core (HL) on the Hurleg Lake in the northeast TP. We aim to determine the reservoir effect and establish an accurate timescale for the core. The RPI record was constructed by normalizing the natural remanent magnetization after 30 mT alternating field demagnetization with saturation isothermal remanent magnetization (NRM30mT/SIRM). This exhibits a general agreement with other geomagnetic intensity stacks from the world, suggesting that global-scale patterns of geomagnetic paleointensity behavior were also documented in Hurleg Lake sediments. Our RPI record can be adequately matched to RPI references to provide three additional age tie points for the HL core. We then evaluated the reservoir effect and constructed a timescale for the core using chronological controls from both RPI and 14C dating. The estimated RE age was weak below 272 cm, was 2–3 ka at the upper 50 cm, and was inferred to have increased between depths of 272 and 50 cm. Environmental magnetism sequences from core HL display a similar paleoclimatic pattern with records from core HL05-2 and core K-2 both in the Hurleg Lake area, suggesting that correction for the radiocarbon reservoir effect is accurate and timescale of core HL is reliable. Our study further demonstrates that the method of obtaining age control points from RPI is applicable to lake sediments on the TP.

CD4+ T helper cells, especially T helper 17 (TH17) cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on proinflammatory cytokine interleukin 17 (IL-17) and interferon-γ (IFN-γ) production. In this study, we screened BA derivatives and found a BA derivative, SH479, that had a greater inhibitory effect on TH17 differentiation. Our further analysis showed that SH479 had a greater inhibitory effect on TH17 and TH1, and a more stimulatory effect on regulatory T (Treg) cells. To evaluate the effects of SH479 on autoimmune diseases in vivo, we employed the extensively used MS mouse model experimental autoimmune encephalomyelitis (EAE). Our results showed that SH479 ameliorated clinical and histologic signs of EAE in both prevention and therapeutic protocols by regulating the TH17/Treg balance. SH479 dose-dependently reduced splenic lymphocyte proinflammatory factors and increased anti-inflammatory factors. Moreover, SH479 specifically inhibited splenic lymphocyte viability from EAE mice but not normal splenic lymphocyte viability. At the molecular level, SH479 inhibited TH17 differentiation by regulating signal transducer and activator of transcription-3 (STAT3) phosphorylation, DNA binding activity, and recruitment to the Il-17a promoter in CD4+ T cells. Furthermore, SH479 promoted the STAT5 signaling pathway and inhibited the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Together, our data demonstrated that SH479 ameliorated EAE by regulating the TH17/Treg balance through inhibiting the STAT3 and NF-κB pathways while activating the STAT5 pathway, suggesting that SH479 is a potential novel drug candidate for autoimmune diseases including MS.

Purpose To investigate the potential protective effect of novel G protein coupled estrogen receptor (GPER1) against the neurotoxicity induced by NMDA in the mouse retina. Methods We induce retinal ganglion cells (RGCs) toxic injury through intravitreal injection of NMDA or acute ocular hypertension (AOH) induced by anterior chamber infusion with saline. Endogenous ligand 17-β-estradiol (E2), GPER1 agonist (G-1), and E2 with GPER1 antagonist (G-15) or classic estrogen receptor α and β (ERα and ERβ) antagonist tamoxifen (TAM) were subcutaneous administered before NMDA to identify the possible involved receptors. Immunofluorescence staining was performed to explore the survival of RGCs and Muller cell gliosis. TUNEL staining was used to evaluate the RGC apoptosis. The involved molecular pathway was detected via antibody array expression profiling. Results Activation of estrogen receptor by E2 or G-1 could significantly rescue the RGCs injury in NMDA administration. The protective effect was carried exclusively by GPER1 activation. E2 application can still mimicked the protective function when estrogen receptor α and β (ERα and ERβ) blocked by tamoxifen (TAM), while the effects was blocked by GPER1 antagonist G-15. Moreover, the TUNEL positive RGCs and GFAP expression level were both attenuated in G-1 application and the effects could be reversed by G-15. In addition, application of the PI3K/Akt antagonist LY294002 counteracted the effect of G-1. And a number of apoptosis regulatory factors decreased dramatically in the G-1 group, including Bad, Caspase 3, Caspase 7, Smad2, P-53 and TAK1. Also, similar protective effect of G-1 was spotted in acute ocular hypertension (AOH) model. Conclusion Estrogen played a protective role via a novel estrogen receptor, GPER1, instead of classical receptors ERα or ERβ. Activation of GPER1 attenuated RGCs apoptosis and Muller cells gliosis, indicating GPER1 as a potential treatment target in RGCs degeneration diseases.

In this study, closed-system Fischer-Tropsch synthesis was conducted at 380°C and 30 MPa for 72 h with magnetite as a catalyst. The isotopic composition of the closed-system Fischer-Tropsch synthesis gas and the composition of known abiogenic gas were systematically studied, and the deep Songliao Basin gas was also investigated. The results show that closed-system Fischer-Tropsch synthesis of gaseous hydrocarbon isotopes exhibits a partial reverse order, which includes the reverse order of methane and ethane such as δ13C-C1>δ13C-C2<δ13C-C3 and δ2H-C1>δ2H-C2<δ2H-C3. Furthermore, experimental data on the control of NaBH4 content indicates that the carbon isotopes demonstrate a reverse order on condition that the H2/CO2 (mole ratio) is equal to or greater than 4.0; meanwhile, the hydrogen isotopes show a normal order. The deep Songliao Basin hydrocarbon gas component is similar to thermogenic gas and has a trend of a transition to oceanic hydrothermal system abiogenic gas. In addition, the deep Songliao Basin gas isotopic pattern is different from both Lost City and Kidd Creek where the deep Basin gas carbon isotopic pattern has a reverse order, and the hydrogen isotopic pattern has a normal order. Therefore, the deep Basin gas might be a mixture of the oil-type gas and the coal-formed gas, which could be the cause of the isotopic reverse.

The Indian summer monsoon (ISM) significantly influences the climate of southwestern China; however, continuous quantitative temperature reconstructions since the Last Glacial Maximum are rare, which limits our understanding of ISM evolution. In this study, we analyzed the branched glycerol dialkyl glycerol tetraethers (brGDGTs) from a lacustrine sediment core from Qionghai Lake to reconstruct the paleoclimatology of southwestern subtropical China over the past 27.7 kyr. Our results suggest that the brGDGTs in Qionghai Lake sediments were probably sourced from catchment soils, with some contributions from in situ lacustrine production. We found that the temperature of the Last Glacial Maximum and Holocene Climatic Optimum was ~3 °C cooler and ~ 2.5 °C warmer than present-day conditions, respectively, based on brGDGTs-reconstructed mean annual air temperatures (MATs). Generally, temperature and precipitation showed synchronous paleovariability in ISM regions. Moreover, Northern Hemisphere summer insolation was the dominant control on climate variability in ISM regions on the precessional scale, while Atlantic Meridional Overturning Circulation activity, Intertropical Convergence Zone positioning, and glacial boundary conditions (ice sheet extent and sea surface temperature) contributed to climate shifts on millennial timescales.

Knowledge of the chemical weathering history under the subtropical monsoonal climate will help to resolve the discrepancies regarding how climate conditions constrain chemical weathering. Major element and rare earth element (REE) compositions of the Qionghai Lake sediments in Sichuan Province, southwestern China were analyzed, aiming to provide information on sediment source discrimination and history of chemical weathering intensities and its responses to variations of Indian summer monsoon (ISM) and paleoclimate conditions. As revealed by the A-CN-K diagram and other provenance proxies including TiO2/Zr ratio, Th/Sc vs. Zr/Sc and La/Th vs. Hf diagrams, as well as the REE characteristics, the source of Qionghai Lake sediments was felsic rocks. Additionally, these sediments were subjected to small changes in provenance, sedimentary sorting and recycling, and weak diagenesis after deposition and/or metasomatism, indicating original signals were maintained on the intensity of chemical weathering of source area. The chemical weathering intensities inferred from CIA (chemical index of alteration) values have significantly fluctuated over the past 28 kyr, reflecting three stages of paleoclimate evolution, which is consistent with grain size characteristics, carbonate contents, low-frequency magnetic susceptibilities, TOC and biomarker proxy (Paq). The CIA values changed significantly during the typical warm and cold climate events including the Last Glacial Maximum, Heinrich 1 cold event, Younger Dryas and Holocene Climatic Optimum, and generally exhibited an increasing trend in amplitude correspondingly, in concert with the climate shifting from cold and dry to warm and humid conditions. Generally warm and humid climate conditions suggest enhanced chemical weathering intensity, whereas weak chemical weathering denotes cold and dry climate in the ISM region. In addition, sequential variations of the CIA values during the past 28 kyr may reflect changing chemical weathering processes, in responses to the varying intensities of Indian summer monsoon and the climate conditions forced by the Northern Hemisphere solar insolation.

The Linxia Basin on the north-eastern Tibetan Plateau in northwest China bears continuous and thick lacustrine-fluvial sediments with environmental significance to central Asian aridification. However, limited efforts have been made on investigating the microbial community evolution, even though lipid biomarkers have been successfully employed to reconstruct paleoenvironmental conditions in this area. This study used the ancient DNA and n-alkanes preserved in the lacustrine-fluvial sediments from the Linxia Basin, and employed high throughput sequencing and geochemical analyses to understand the climatic conditions spanning the past 29 million years. The characteristics of n-alkanes indicate that the organic matter was derived from mixed sources (bacteria, algae, and higher plants), and a series of n-alkane proxies (ACL, n-C21−/n-C22+, Paq, and Pwax) established that the climate shifted to arid conditions at approximately 8 Ma. It is noteworthy that the relative abundance trends of two classes of microbes (Proteobacteria and Firmicutes) were negatively correlated. Furthermore, the increasing Firmicutes and the relatively decreasing Proteobacteria at approximately 8 Ma also corroborated this arid event. In addition, during this period, there was an extremely low abundance of archaea, which might correspond to severe climatic conditions around 8 Ma. Therefore, this study suggests that the microbial communities could serve as a potential tool for the reconstruction of paleoenvironments.