Characterization of the incense sacrificed to the sarira of Sakyamuni from Famen Royal Temple during the ninth century in China.

SignificanceIncense has been linked to ceremonies, religions, medicines, and cosmetics worldwide for thousands of years. While Chinese texts in the Tang dynasty (618 to 907 CE) indicate that numerous exotic aromatic substances were already being introduced into China through the land and maritime Silk Road, this has been rarely demonstrated archaeologically. This study identifies three types of incense associated with the sacred sarira of Sakyamuni Budda from the underground palace of Famen Royal Temple in central China, providing direct evidence of aromatics including elemi, agarwood, and frankincense as well as their composite product, namely Hexiang (blending of aromatics), in Buddhist activities, which may have promoted the spread of incense and the development of aromatic knowledge systems in medieval China.

[C(NH2)3]6Mo7O24: A Guanidinium Molybdate as a UV Nonlinear Optical Crystal with Large Birefringence.

The key to searching novel nonlinear optical (NLO) crystals was effectively combining the NLO-active units to obtain a noncentrosymmetric structure. Nevertheless, the present predicament lies in the growing challenge of discovering novel crystals within conventional inorganic frameworks that surpass the properties of the current NLO materials. In view of this, researchers expanded their research focus to the organic-inorganic hybridization system; it is foreseeable to concentrate the advantages from several kinds of NLO-active units to acquire novel NLO crystals with superior properties. We herein report an organic-inorganic hybrid molybdate crystal, namely, [C(NH2)3]6Mo7O24 (GMO). It was successfully obtained via combining inorganic NLO-active MoO6 octahedra and organic π-conjugated [C(NH2)3]+ groups. GMO demonstrates a moderate second-harmonic-generation response, specifically measuring about 1.3 times the value of KDP. Additionally, it exhibits a significant birefringence value of 0.203 at the wavelength of 550 nm and possesses a wide band gap of 3.31 eV. Theoretical calculations suggest that the optical properties of the GMO are primarily influenced by the synergy effect of [C(NH2)3]+ groups between MoO6 octahedra.

[C(NH2)3][B(C2O2H4)2]: An Organic-Inorganic Hybrid Borate Containing Nonlinear-Optical Active Unit [B(C2O2H4)2]- with Solar-Blind-Region Optical Nonlinearity.

We herein report an unprecedented organic-inorganic hybrid borate incorporating a novel nonlinear-optical (NLO) active unit, namely, [C(NH2)3][B(C2O2H4)2]. The novel NLO active unit was derived from the condensation reaction between two glycol molecules and one (BO4)5- group. The title compound exhibits a moderate second-harmonic-generation effect (0.7 × KDP), a significant band gap (5.76 eV), and a suitable birefringence (0.078 at 550 nm). The optical properties are determined by the synergistic interaction between the C(NH2)3+ cation and the [B(C2O2H4)2]- group, as indicated by theoretical calculations.

Isolation Techniques, Structural Characteristics, and Pharmacological Effects of Phellinus Polysaccharides: A Review.

Phellinus is a precious perennial medicinal fungus. Its polysaccharides are important bioactive components, and their chemical composition is complex. The polysaccharides are mainly extracted from the fruiting body and mycelium. The yield of the polysaccharides is dependent on the extraction method. They have many pharmacological activities, such as antitumor, immunomodulatory, antioxidant, hypoglycemic, anti-inflammatory, etc. They are also reported to show minor toxic and side effects. Many studies have reported the anticancer activity of Phellinus polysaccharides. This review paper provides a comprehensive examination of the current methodologies for the extraction and purification of Phellinus polysaccharides. Additionally, it delves into the structural characteristics, pharmacological activities, and mechanisms of action of these polysaccharides. The primary aim of this review is to offer a valuable resource for researchers, facilitating further studies on Phellinus polysaccharides and their potential applications.

Negative Lattice Expansion in an O3-Type Transition-Metal Oxide Cathode for Highly Stable Sodium-Ion Batteries.

The sodium extraction/insertion in layered transition-metal oxide (TMO) cathode materials are typically accompanied by slab sliding and lattice changes, leading to microstructure destruction and capacity decay. Herein, negative lattice expansion is observed in an O3 type Ni-based layered cathode of Na0.9 Ni0.32 Zn0.08 Fe0.1 Mn0.3 Ti0.2 O2 upon Na+ extraction. It is attributed to the weak Zn2+ -O2- orbital hybridization and increased electron density of the surrounding oxygen for reinforced interlayer O-O repulsive force. This enables gliding of TMO slabs for the intergrowth phase transition of P3→OP2 to alleviate lattice strain with moderate lattice shrinkage, which exhibits general interslab spacings and volume changes as low as 2.4 % and 1.9 %, respectively. The strong Ti-O bonds accommodate the internal distortion of TMO6 octahedra due to the flexibility of TiO6 octahedra during cycling. These endow a high specific capacity of 144.9 mAh g-1 and excellent cycling performance of pouch-type sodium-ion batteries with 93 % capacity retention after 3600 cycles.

Slow development allows redundant genes to restore the fertility of rpg1, a TGMS line in Arabidopsis.

Slow development has been shown to be a general mechanism to restore the fertility of thermo-sensitive and photoperiod-sensitive genic male sterile (TGMS and PGMS) lines in Arabidopsis. rpg1 is a TGMS line defective in primexine, which is essential for pollen wall pattern formation. Here, we showed that RPG1-GFP was highly expressed in microsporocytes, microspores, and pollen grains but not in the tapetum in the complemented transgenic line, suggesting that microsporocytes are the main sporophytic cells for primexine formation. Further cytological observations showed that primexine formation in rpg1 was partially restored under slow growth conditions, leading to its fertility restoration. RPG2 is the homolog of RPG1 in Arabidopsis. We revealed that the fertility recovery of rpg1 rpg2 was significantly reduced compared with that of rpg1 under low temperature. The RPG2-GFP protein was also expressed in microsporocytes in the RPG2-GFP (WT) transgenic line. These results suggest that RPG2 plays a redundant role in rpg1 fertility restoration. rpg1 plants were male sterile at the early growth stage, while their fertility was partially restored at the late developmental stage. The fertility of the rpg1 lateral branches was also partially restored. Further growth analysis showed that slow growth at the late reproductive stage or on the lateral branches led to fertility restoration. This work reveals the importance of gene redundancy in fertility restoration for TGMS lines and provides further insight into pollen wall pattern formation.

Myth behind Metastable and Stable n-Hexylammonium Bromide-Based Low-Dimensional Perovskites.

In perovskite solar cells, passivating the surface or interface that contains a high concentration of defects, specifically deep-level defects, is one of the most important topics to substantially enhance the power conversion efficiency and stability of the devices. Long-chain alkylammonium bromides have been widely and commonly adapted for passivation treatment. However, the mechanism behind is still not well explored as the formation route and the exact structure of these alkylammonium bromide-based low-dimensional perovskites are unclear. Herein, we investigate the physical and chemical properties of an n-hexylammonium bromide (HABr)-based low-dimensional perovskite including both thin films and single crystals. First of all, the HA2PbBr4 perovskite film and aged single crystal demonstrate different X-ray diffraction patterns from those of the fresh as-prepared single crystal. We found that the fresh HA2PbBr4 single crystal exhibits a metastable phase as its structure changes with aging due to the relaxation of crystal lattice strains, whereas the HA2PbBr4 perovskite film is pretty stable as the aged single crystal. Upon reacting with FAPbI3, HABr can be intercalated into the FAPbI3 lattice to form a mixed-cation perovskite of HAFAPbI3Br, which is in a dynamic equilibrium of decomposition and formation. In contrast, the reaction of HABr with excess PbI2 forms a stable HA2PbI2Br2 perovskite. Based on such findings, we rationally develop a HA2PbI2Br2-passivated FACs-based perovskite by reacting HABr with excess PbI2, the photovoltaics based on which are more stable and efficient than those passivated by the HAFAPbI3Br perovskite. Our discovery paves way for a more in-depth study of bromide-containing low-dimensional perovskites and their optoelectronic applications.

Homeostatic Solid Solution in Layered Transition-Metal Oxide Cathodes of Sodium-Ion Batteries.

Two-phase transformation reaction is ubiquitous in solid-state electrochemistry; however, it usually involves inferior structure rearrangement upon extraction and insertion of large-sized Na+, thus leading to severe local strain, cracks, and capacity decay in sodium-ion batteries (SIBs). Here, a homeostatic solid solution reaction is reported in the layered cathode material P'2-Na0.653Ni0.081Mn0.799Ti0.120O2 during sodiation and desodiation. It is induced by the synergistic incorporation of Ni and Ti for the reinforced O(2p)-Mn(3d-eg*) hybridization, which leads to mitigated Jahn-Teller distortion of MnO6 octahedra, contracted transition-metal oxide slabs, and enlarged Na layer spacings. The thermodynamically favorable solid solution pathway rewards the SIBs with excellent cycling stability (87.2% capacity retention after 500 cycles) and rate performance (100.5 mA h g-1 at 2500 mA g-1). The demonstrated reaction pathway will open a new avenue for rational designing of cathode materials for SIBs and beyond.

Fibroblast-Derived Extracellular Vesicle-Packaged Long Noncoding RNA Upregulated in Diabetic Skin Enhances Keratinocyte MMP-9 Expression and Delays Diabetic Wound Healing.

Accurate communication between fibroblasts and keratinocytes is crucial for diabetic wound healing. Extracellular vesicles are being explored as essential mediators of intercellular communication in the skin. However, the mechanisms underlying wound healing mediated by fibroblast-derived extracellular vesicles (Fib-EVs) remain unclear. The present study evaluated the role of long noncoding RNA upregulated in diabetic skin (lnc-URIDS) packed in Fib-EVs in the wound healing of streptozotocin-induced diabetes and the potential mechanisms of the effects. We demonstrated that high glucose induced the enrichment of lnc-URIDS in Fib-EVs, facilitated the transfer of lnc-URIDS to primary rat epidermal keratinocytes, and increased the expression of matrix metalloproteinase-9. Mechanistically, the binding of lnc-URIDS to YTH domain family protein-2 enhanced the degradation of YTH domain family protein-2 in the lysosomes, which increased the translational activity of the messenger RNA of matrix metalloproteinase-9 and ultimately induced the degradation of collagen for wound healing. The results provided an insight into the crosstalk and cooperation between fibroblasts and keratinocytes in collagen homeostasis in diabetic wounds and clarified the mechanism by which lnc-URIDS degrades collagen for diabetic wound healing.

Internal Electric Field-Modulated Charge Migration Behavior in MoS2 /MIL-53(Fe) S-Scheme Heterojunction for Boosting Visible-Light-Driven Photocatalytic Chlorinated Antibiotics Degradation.

Inadequate photo-generated charge separation, migration, and utilization efficiency limit the photocatalytic efficiency. Herein, a MoS2 /MIL-53(Fe) photocatalyst/activator with the S-scheme heterojunction structure is designed and the charge migration behavior is modulated by the internal electric field (IEF). The IEF intensity is enhanced to 40 mV by modulating band bending potential and the depletion layer length of MoS2 . The photo-generated electron migration process is boosted by constructing the electron migration bridge (Fe-O-S) and modulating the IEF as the driving force, confirmed by the density functional theory calculation. Compared with the pristine materials, the photocurrent density of MoS2 /MIL-53(Fe) is significantly enhanced 27.5 times. Contributed by the visible-light-driven cooperative catalytic degradation and the high-efficiency direct photo-generated electron reduction dichlorination process, satisfactory chlorinated antibiotics removal and detoxification performances are achieved. This study opens up new insights into the application of heterojunctions in photocatalytic activation of PDS in environmental remediation.

Whole-Voltage-Range Solid-Solution Reaction in Layered Oxide Cathode of Sodium-Ion Batteries.

Layered manganese-based oxides (LMOs) are promising cathode materials for sodium-ion batteries (SIBs) due to their versatile structures. However, the Jahn-Teller effect of Mn3+ induces severe distortion of MnO6 octahedra, and the resultant low symmetry is responsible for the gliding of MnO2 layers and then inferior multiple-phase transitions upon Na+ extraction/insertion. Here, hexagonal P2-Na0.643 Li0.078 Mn0.827 Ti0.095 O2 is synthesized through the incorporation of Li and Ti into the distorted orthorhombic P'2-Na0.67 MnO2 to function as a phase-transition-free oxide cathode. It is revealed that Li in both the transition-metal and Na layers enhances the covalency of Mn-O bonds and allows degeneracy of Mn 3d eg orbitals to favor the formation of hexagonal phase, and the high strength of Ti-O bonds reduces the electrostatic interaction between Na and O for suppressed Na+ /vacancy rearrangements. These collectively lead to a whole-voltage-range solid-solution reaction between 1.8 and 4.3 V with a small volume variation of 1.49%. This rewards its excellent cycling stability (capacity retention of 90% after 500 cycles) and rate capability (89 mAh g-1 at 2000 mA g-1 ).

Psychiatric disorders and Type 2 diabetes mellitus: A bidirectional Mendelian randomization.

BACKGROUND: Extensive observational evidence put forward the association between psychiatric disorders and type 2 diabetes mellitus (T2DM). However, causal relationships between these two diseases required further research. Thus, we evaluated the bidirection casual effect between five psychiatric disorders and T2DM using two-sample mendelian randomization (MR). METHODS: By selecting single nucleotide polymorphisms associated with T2DM and five psychiatric disorders (attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia, anxiety disorder and panic disorder), a bidirectional two-sample MR was applied to evaluate causality between these diseases. The inverse-variance weighted (IVW) method was used as the primary analysing approach for estimating possible causal effects. MR-Egger and weighted median were also conducted to verify the results. The funnel plot, Cochran's Q test and MR-Egger intercept test were used for sensitivity analyses. In addition, potential mediators were investigated by risk factor analyses. RESULTS: Genetic susceptibilities of ADHD and MDD would increase the risk of T2DM (ADHD: OR = 1.14, 95%CI 1.08-1.20; p = 5.7 × 10 - 6 ; MDD: OR = 1.22, 95%CI 1.09-1.36; p = 0.0004 ). In addition, genetic predisposition to T2DM was also associated with ADHD (OR = 1.09, 95%CI 1.04-1.14; p = 0.0004). Several risk factors of T2DM were implicated in the above causal associations, including smoking, high body mass index, waist-to-hip ratio and elevated serum triglycerides. CONCLUSION: Our studies indicated a causal effect of ADHD and MDD on increasing the risk of T2DM, which was potentially mediated by smoking and obesity-related phenotypes. Meanwhile, we found a causal effect of T2DM on ADHD. Thus, prevention strategies for T2DM should also include mental health and vice versa.

The prognostic utility of preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with colorectal liver metastasis: a systematic review and meta-analysis.

The neutrophil-to-lymphocyte ratio is used to reflect body's inflammatory status with prognostic value in different cancers. We aimed to investigate the influence of preoperative NLR in the prognosis of CRLM patients receiving surgery using meta-analysis. Data in Cochrane Library, PubMed, Embase, and Web of Science databases created before October 2022 were recruited. Meta-analysis was carried out with RevMan 5.3 and Stata16 software, and the primary outcome indicators included overall survival (OS), and secondary outcome indicators included disease-free survival (DFS) and relapse-free survival (RFS). The pooled risk ratio (HR) and 95% confidence interval (CI) for each outcome indicator were determined using random-effects models or fixed-effects models. The pooled odds ratio (OR) and corresponding 95% confidence intervals (CI) for NLR and clinicopathological characteristics were determined with a fixed-effects model. 18 papers published between 2008 and 2022 (3184 patients in total) were included. The pooled analysis found that high preoperative NLR was correlated with poor OS (multivariate HR = 1.83, 95% CI = 1.61-2.08, p < 0.01), DFS (multivariate HR = 1.78, 95% CI = 1.16-2.71, p < 0.01) and RFS (multivariate HR = 1.46, 95% CI = 1.15-1.85, p < 0.01), but NLR was not related to clinicopathological features of CRLM patients correlation. In conclusion, NLR is an independent risk factor for poor prognosis in patients with CRLM. More large-scale clinical researches are required in the future to demonstrate the inclusion of preoperative NLR as a prognostic indicator for CRLM patients to guide postoperative adjuvant chemotherapy.

C(NH2)3(I3O8)(HI3O8)(H2I2O6)(HIO3)4·3H2O: An Unprecedented Asymmetric Guanidinium Polyiodate with a Strong Second-Harmonic-Generation Response and a Wide Band Gap.

Herein, we report an unprecedented asymmetric guanidinium polyiodate, namely, C(NH2)3(I3O8)(HI3O8)(H2I2O6)(HIO3)4·3H2O (1). The title compound was obtained via the hybridization of polyiodate anions and planar π-conjugated C(NH2)3+; meanwhile, its strong second-harmonic-generation (SHG) response (2.1 × KDP, where KDP = KH2PO4) and wide band gap (3.89 eV) were mainly dominated by the synergy effect of the aforementioned structural units.

[C(NH2)2NHNO2][C(NH2)3](NO3)2: A Mixed Organic Cationic Hybrid Nitrate with an Unprecedented Nonlinear-Optical-Active Unit.

We herein report a mixed organic cationic hybrid nitrate, namely, [C(NH2)2NHNO2][C(NH2)3](NO3)2 (1). It was successfully achieved via combining three different planar groups: [(C(NH2)2NHNO2]+, C(NH2)3+, and NO3-. First-principles calculations confirm that the [(C(NH2)2NHNO2]+ group is an excellent cationic nonlinear-optical (NLO)-active unit. The title compound exhibits a moderate second-harmonic-generation (SHG) response (1.5 × KDP), a wide band gap (3.58 eV), and a suitable birefringence of 0.071 at 550 nm. Theoretical calculations indicate that the synergy effect between the [(C(NH2)2NHNO2]+ and C(NH2)3+ groups dominates the SHG process.

The association of FGF-21 with the risk of newly diagnosed type-2 diabetes mellitus: a cross-sectional study in Southern China.

BACKGROUND: This study investigated the relationship between fibroblast growth factor 21 (FGF-21) and newly diagnosed type-2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study, FGF-21 and T2DM risk were analyzed using restricted cubic splines with univariate or multivariate logistic regression analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via logistic regression analysis. Cluster and subgroup analyses were conducted to evaluate the associations between FGF-21 and diabetes in different subpopulations. Nomograms and ROC curves were used to explore the clinical utility of FGF-21 in the diabetes assessment model. RESULTS: High levels of FGF-21 were significantly associated with a high risk of T2DM after adjusting for confounding factors in both the total population and subpopulations (P for trend < 0.001). In the total population, the ORs of diabetes with increasing FGF-21 quartiles were 1.00 (reference), 1.24 (95% CI 0.56-2.80; quartile 2), 2.47 (95% CI 1.18-5.33; quartile 3), and 3.24 (95% CI 1.53-7.14; quartile 4) in Model 4 (P < 0.001), and the trend was consistent in different subpopulations. In addition, compared with the model constructed with conventional noninvasive indicators, the AUC of the model constructed by adding FGF-21 was increased from 0.668 (95% CI: 0.602-0.733) to 0.715 (95% CI: 0.654-0.777), indicating that FGF-21 could significantly improve the risk-assessment efficiency of type-2 diabetes. CONCLUSION: This study demonstrated that a high level of circulating FGF-21 was positively correlated with diabetes, and levels of FGF-21 could be an important biomarker for the assessment of diabetes risk.

Silk fibroin fibers-based shape memory membrane with Janus wettability for multitiered wearable protection.

Realizing breathable shape memory fiber-based material with antibacterial and waterproof performances is important for multitiered wearable protection to address the increasing concerns of air pollution. Herein, using an alternating electrospinning-electrospraying technology, we develop a fiber-based membrane with Janus wettability based on a silk fibroin nanofibers-substrate (SFNFs), a polyurethane nanospheres-top layer (PUNSs), and a middle layer of PU nanofibers-mat with in-situ grown silver nanoparticles (PUNFs-AgNPs), which serves separately for skin contact, a self-cleaning physical barrier to resist external aerosol/bacteria (PM2.5 filtration efficiency ~ 98.1%), and a bio-barrier that can sterilize harmful particles and inhibit bacteria proliferation (> 95%). This breathable Janus film (SFNFs/PUNFs-AgNPs/PUNSs, SPAP) with an antibacterial filter shows shape memory stretchability enabled by the thermoplastic PU component, which is mechanically adaptive to human body for wearable protection. This work presents a breathable wearable material for air-filtration and anti-bacteria, promising for applications such as wound dressings, medical masks, protection suits, and multifunctional filters. Graphical abstract: An alternating electrospinning-electrospraying technology was proposed to achieve a silk fibroin-based antibacterial membrane with Janus wettability, as well as good skin affinity and breathability, which serves well as physical and bio-barriers for water resistance, PM2.5 filtration (~98.1%) and bacteria inhibition (efficiency of 95%). This shape memory Janus membrane can adapt mechanically to human body curvatures for functional wearable protections. Supplementary Information: The online version contains supplementary material available at 10.1557/s43578-022-00805-w.

Lung cancer risk and exposure to air pollution: a multicenter North China case-control study involving 14604 subjects.

BACKGROUND: For North Chinese lung cancer patients, there is limited study on the distribution of air pollution and smoking related features based on analyses of large-scale, high-quality population datasets. The aim of the study was to fully analyze risk factors for 14604 Subjects. METHODS: Participants and controls were recruited in 11 cities of North China. Participants' basic information (sex, age, marital status, occupation, height, and weight), blood type, smoking history, alcohol consumption, history of lung-related diseases and family history of cancer were collected. PM2.5 concentration data for each year in each city of the study area from 2005 to 2018 were extracted based on geocoding of each person's residential address at the time of diagnosis. Demographic variables and risk factors were compared between cases and matched controls using a univariate conditional logistic regression model. Multivariate conditional logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for risk factors in univariate analysis. The nomogram model and the calibration curve were developed to predict lung cancer probability for the probability of lung cancer. RESULTS: There was a total of 14604 subjects, comprising 7124 lung cancer cases and 7480 healthy controls included in the study. Marital status of unmarried persons, people with a history of lung-related disease, corporate personnel and production /service personnel were protective factors for lung cancer. People younger than 50 years old, people who were smoking and quit smoking, people who had been drinking consistently, people with family history of cancer and PM2.5 exposure were proven to be a risk factor for lung cancer. The risk of lung cancer varied with sex, smoking status and air pollution. Consistent alcohol consumption, persistent smoking and smoking quit were risk factors for lung cancer in men. By smoking status, male was risk factor for lung cancer in never smokers. Consistent alcohol consumption added risk for lung cancer in never smokers. The combined effects of PM2.5 pollution exposure and ever smoking aggravated the incidence of lung cancer. According to air pollution, lung cancer risk factors are completely different in lightly and heavily polluted areas. In lightly polluted areas, a history of lung-related disease was a risk factor for lung cancer. In heavily polluted areas, male, consistent alcohol consumption, a family history of cancer, ever smokers and smoking quit were all risk factors for lung cancer. A nomogram was plotted and the results showed that PM2.5 was the main factor affecting the occurrence of lung cancer. CONCLUSIONS: The large-scale accurate analysis of multiple risk factors in different air quality environments and various populations, provide clear directions and guidance for lung cancer prevention and precise treatment.

Early evidence for mounted horseback riding in northwest China.

Horseback riding was a transformative force in the ancient world, prompting radical shifts in human mobility, warfare, trade, and interaction. In China, domestic horses laid the foundation for trade, communication, and state infrastructure along the ancient Silk Road, while also stimulating key military, social, and political changes in Chinese society. Nonetheless, the emergence and adoption of mounted horseback riding in China is still poorly understood, particularly due to a lack of direct archaeological data. Here we present a detailed osteological study of eight horse skeletons dated to ca. 350 BCE from the sites of Shirenzigou and Xigou in Xinjiang, northwest China, prior to the formalization of Silk Road trade across this key region. Our analyses reveal characteristic osteological changes associated with equestrian practices on all specimens. Alongside other relevant archaeological evidence, these data provide direct evidence for mounted horseback riding, horse equipment, and mounted archery in northwest China by the late first millennium BCE. Most importantly, our results suggest that this region may have played a crucial role in the spread of equestrian technologies from the Eurasian interior to the settled civilizations of early China, where horses facilitated the rise of the first united Chinese empires and the emergence of transcontinental trade networks.

Recent anthropogenic curtailing of Yellow River runoff and sediment load is unprecedented over the past 500 y.

The Yellow River (YR) is the fifth-longest and the most sediment-laden river in the world. Frequent historical YR flooding events, however, have resulted in tremendous loss of life and property, whereas in recent decades YR runoff and sediment load have fallen sharply. To put these recent changes in a longer-term context, we reconstructed natural runoff for the middle reach of the YR back to 1492 CE using a network of 31 moisture-sensitive tree-ring width chronologies. Prior to anthropogenic interference that started in the 1960s, the lowest natural runoff over the past 500 y occurred during 1926 to 1932 CE, a drought period that can serve as a benchmark for future planning of YR water allocation. Since the late 1980s, the low observed YR runoff has exceeded the natural range of runoff variability, a consequence of the combination of decreasing precipitation and increasing water consumption by direct and indirect human activities, particularly agricultural irrigation. This reduced runoff has resulted in an estimated 58% reduction of the sediment load in the upper reach of the YR and 29% reduction in the middle reach.