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Microproteomics, the profiling of protein expressions in small cell populations or individual cells, is essential for understanding complex biological systems. However, sample loss and insufficient sensitivity of analytical techniques pose severe challenges to this field. Microfluidics, particularly droplet-based microfluidics, provides an ideal approach by enabling miniaturized and integrated workflows to process samples and offers several advantages, including reduced sample loss, low reagent consumption, faster reaction times, and improved throughput. Droplet-based microfluidics manipulates droplets of fluids to function as discrete reaction units, enabling complex chemical reactions and biological workflows in a miniaturized setting. This article discusses a variety of on-chip functions of droplet-based microfluidics, including cell sorting, cell culture, and sample processing. We then highlight recent advances in the mass spectrometry (MS)-based analysis of single cells using droplet-based microfluidic platforms, including digital microfluidics (DMF). Finally, we review the integrated DMF–MS systems that enable automated and parallel proteomic profiling of single cells with high sensitivity and discuss the applications of the technology and its future perspectives.

Vascular tissue engineering faces significant challenges in creating in vitro vascular disease models, implantable vascular grafts, and vascularized tissue/organ constructs due to limitations in manufacturing precision, structural complexity, replicating the composited architecture, and mimicking the mechanical properties of natural vessels. Light-based 3D bioprinting, leveraging the unique advantages of light including high resolution, rapid curing, multi-material adaptability, and tunable photochemistry, offers transformative solutions to these obstacles. With the emergence of diverse light-based 3D bioprinting techniques and innovative strategies, the advances in vascular tissue engineering have been significantly accelerated. This review provides an overview of the human vascular system and its physiological functions, followed by an in-depth discussion of advancements in light-based 3D bioprinting, including light-dominated and light-assisted techniques. We explore the application of these technologies in vascular tissue engineering for creating in vitro vascular disease models recapitulating key pathological features, implantable blood vessel grafts, and tissue analogs with the integration of capillary-like vasculatures. Finally, we provide readers with insights into the future perspectives of light-based 3D bioprinting to revolutionize vascular tissue engineering.

In three studies, we investigated how League of Legends (LOL) game experience and game skill relate to players' performance in the Iowa Gambling Task (IGT), Balloon Analogue Risk Task (BART), and Probability Discounting Task (PDT). Additionally, the present study examined the relationship between players' in-game risk preferences and their performance in three types of decision-making tasks. To achieve this, we utilized a self-developed League of Legends Risk Propensity Scale (LRPS) to characterize LOL players' in-game risk preferences. The LRPS demonstrated appropriate reliability and validity in this study. Overall, our results indicated that the differences between LOL players' and non-players' decision-making performance were significant only in the PDT. Moreover, among LOL players, the relationship between game skill and decision-making performance was significant in the IGT (especially in the last sixty trials) and the PDT, but not in the BART. Furthermore, LRPS scores could predict performance in the PDT, but not in the IGT or BART. Our results suggest that experience and game skill in LOL are primarily linked to players' performance in risky decision-making tasks. Similarly, participants' in-game risk preferences in LOL are only related to their performance in the risky decision-making process, not in the ambiguous decision-making process. We propose that LOL players' in-game ambiguous decision-making processes may exhibit domain-specific characteristics.

Summary: Arterial disorders such as atherosclerosis, thrombosis, and aneurysm pose significant health risks, necessitating advanced interventions. Despite progress in artificial blood vessels and animal models aimed at understanding pathogenesis and developing therapies, limitations in graft functionality and species discrepancies restrict their clinical and research utility. Addressing these issues, bioengineered arterial equivalents (AEs) with enhanced vascular functions have been developed, incorporating innovative technologies that improve clinical outcomes and enhance disease progression modeling. This review offers a comprehensive overview of recent advancements in bioengineered AEs, systematically summarizing the bioengineered technologies used to construct these AEs, and discussing their implications for clinical application and pathogenesis understanding. Highlighting current breakthroughs and future perspectives, this review aims to inform and inspire ongoing research in the field, potentially transforming vascular medicine and offering new avenues for preclinical and clinical advances.

Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) of high toxicity and also are shared active toxic intermediates of multiple halogenated organic pollutants. Due to the strong oxidizing property and electrophilicity, HBQs exhibit extremely diverse metabolism pathways in organisms. The identification of toxic-decisive metabolites is pivotal, albeit challenging, for understanding the toxicity mechanisms of HBQs. We employed dibromo-benzoquinone (DBBQ) as a representative HBQ, and established a systematic analytical strategy using high-resolution mass spectrometry, which collectively coupled suspect screening (SS), mass defect filtering (MDF), product ion filtering (PIF), isotopic signature filtering (ISF), and molecular networking (MN). As a result, 20 biotransformation products of DBBQ were identified in vivo and in vitro, involving metabolism reactions such as hydroxylation, methylation, methoxylation, acetylation, sulfonation, glucuronidation, glutathionylation, dimerization, and conjugation with amino acids or fatty acids. Quantitative structure-activity relationship (QSAR) analysis and cytotoxicity experiments consistently demonstrated the significantly high toxicity of the fatty acid conjugate compared to the parent compound DBBQ and other metabolites, pinpointing the important role of the fatty acid conjugation in determining the metabolism and toxicity of HBQs. The research conducted a comprehensive evaluation of the metabolism of a typical HBQ with the combination of multiple analytical and toxicity characterization methods, therefore screen out the most important metabolism pathway of HBQs.

Social animals frequently exhibit huddling sleep behaviors in response to nocturnal ecological pressures. However, there remain significant gaps in our understanding of the decision-making process promoting huddle sleep. Exploring how such decision-making processes are initiated and programmed in nonhuman primates offers additional insights into various animals, with a particular focus on humans. The present research examined the social factors and individual influences involved in initiating huddle sleep among a population of wild Tibetan macaques (Macaca thibetana) at Mt. Huangshan in Anhui, China. The results showed that social rank, age, and social centrality were involved in the decision-making process for huddle sleep. Individuals with higher rank and greater social centrality not only tended to act as leaders but also frequently took on followers. Younger individuals were more inclined to be followers. If an individual consistently followed a specific member during huddles, we referred to her/him as a fan. Individuals with more fans (fandom) and those that were consistently fans of others were also more socially central in their group. Such different selection factors fostered coordination among individuals and promoted huddle formation. The study has enhanced our understanding of nocturnal huddling behavior in social nonhuman primates and the intricate mechanisms involved in decision-making. The findings provide valuable insights into the sleep behavior of wild animals, thereby increasing our understanding of how monkeys maintain long-term survival. The analysis of sleep behavior has significant theoretical and practical implications for the conservation of Tibetan macaques.

Creation of novel fluorescent nanomaterials with high photoluminescence quantum yield (PLQY) will lead to high-efficiency luminescent solar concentrators (LSCs). Herein, two kinds of carbon dots (CDs), e.g., blue and green emissive CDs and one novel carbon nanorings (NRs) with yellow emission are synthesized by the solvothermal method. Diaminobenzenesulfonic acid is used as one main precursor to create blue, green emission carbon dots (B/GCDs) and yellow emission carbon nanorings (YCNRs). Importantly, the PLQYs of B/GCDs and YCNRs are 59.8±3.2 %, 12.2±0.7 % and 63.2±1.5 %, respectively. Moreover, B/GCDs and YCNRs are used as fluorescent nanomaterials to construct laminated LSCs with single-layer and double-layer through one-step photopolymerization technique. For single-layer laminated LSCs, YCNRs-based LSCs have the maximum external optical efficiency (ηopt), up to 3.05 %. Furthermore, for double-layer laminated LSCs, the LSCs based on BCDs and YCNRs achieve the highest ηopt of 4.09 %. Compared to single-layer laminated LSCs, the double-layer laminated LSCs show an increase of 34 % in ηopt. Their internal quantum efficiency (ηint) of 29.88 % and external quantum efficiency (ηext) of 25.18 % are obtained, respectively. The presented values are just for single-wavelength excitation. Thus, the synthesis of novel YCNRs with high PLQYs contributes to the optical performances at a large level. Remarkably, the optimal double-layer laminated LSCs show good transparency.

The utilization of vanadium titano-magnetite concentrate (VTM) for pellet preparation poses challenges in terms of low consolidation strength and high energy consumption during the thermal process. The effect and function mechanism of high-pressure grinding roll (HPGR) pretreatment on the preparation of VTM pellets were investigated. The results indicate that HPGR pretreatment increased the strength of the pellets prepared by VTM and decreased the thermal processing temperature and time. The main reason can be attributed to the reduced particle size of VTM, accompanied by an increase in specific surface area, iron-bearing mineral liberation, and improved interfacial hydrophilicity and particle ballability. Moreover, HPGR pretreatment reduced the crystallite size of VTM and increased lattice microstrain and amorphousness, leading to a 13.21 kJ/mol improvement in the mechanical energy storage of titanomagnetite. The increased specific surface area was a crucial factor in strengthening the preparation of VTM pellets, which increased the contacting points participated in interface physicochemical reactions. The enhanced hydrophilicity and ballability were beneficial to improving the strength of green pellets, while the increased strength of roasted pellets was primarily attributed to the iron-containing mineral liberation and crystal mechanical activation, which promoted the oxidation of iron-bearing minerals and the microcrystalline diffusion and connection. Compared with the untreated VTM, the compressive strength of roasted pellets increased from 2168 N P−1 (Newton per pellet) to 2813 N P−1 when the roller pressure intensity was 12 MPa, and the proper roasting temperature could be reduced by more than 50 °C.

Mitotic kinesin-like protein 2 (MKLP2/KIF20A) is a key mitotic regulator frequently overexpressed in human malignancies and its abundance is positively correlated with poor outcomes of the disease. Despite extensive research on MKLP2 as a potential target for oncology, the development of small-molecule inhibitors specific to MKLP2 remains limited. We have previously identified a benzoazipinone compound, HJ81 as a potent disruptor of Aurora kinase B (AURKB) localization during late mitosis. This study reveals that such disruption results from a failure of AURKB relocation at the onset of anaphase and this phenomenon can be specifically attributed to the disablement of MKLP2, a recognized facilitator of the relocation process. Further optimization of HJ81 leads to identifying compounds such as 12a as promising lead inhibitors of MKLP2-mediated processes, with improved pharmacokinetic properties. 12a inhibits the microtubule-stimulated ATPase activity of the recombinant MKLP2 in vitro. Significant suppression of tumor growth was observed in mice bearing the Calu-6 lung cancer cell line when treated with 12a at a well-tolerated dose. Overall, our findings suggest that benzoazipinone derivatives represent a novel chemical scaffold with the potential to be developed to mimic MKLP2 inhibition for cancer treatment.

Hydrogen peroxide (H2O2) in situ electrosynthesis by O2 reduction reaction is a promising alternative to the conventional Fenton treatment of refractory wastewater. However, O2 mass transfer limitation, cathodic catalyst selectivity, and electron transfer in O2 reduction remain major engineering obstacles. Here, we have proposed a systematic solution for efficient H2O2 generation and its electro-Fenton (EF) application for refractory organic degradation based on the fabrication of a novel ZrO2/CMK-3/PTFE cathode, in which polytetrafluoroethylene (PTFE) acted as a hydrophobic modifier to strengthen the O2 mass transfer, ZrO2 was adopted as a hydrophilic modifier to enhance the electron transfer of O2 reduction, and mesoporous carbon CMK-3 was utilized as a catalyst substrate to provide catalytic active sites. Moreover, feasible mass transfer of O2 from the hydrophobic to the hydrophilic layer was designed to increase the contact between O2 and the reaction interface. The H2O2 yield of the ZrO2/CMK-3/PTFE cathode was significantly improved by approximately 7.56 times compared to that of the conventional gas diffusion cathode under the same conditions. The H2O2 generation rate and Faraday efficiency reached 125.98 mg·cm−2·h−1 (normalized to 5674.04 mmol·g−1·h−1 by catalyst loading) and 78.24% at −1.3 V versus standard hydrogen electrode (current density of −252 mA·cm−2), respectively. The high H2O2 yield ensured that sufficient OḢ was produced for excellent EF performance, resulting in a degradation efficiency of over 96% for refractory organics. This study offers a novel engineering solution for the efficient treatment of refractory wastewater using EF technology based on in situ high-yield H2O2 electrosynthesis.

The distribution and migration routes of the most studied swan species, mute swans (Cygnus olor), in East Asia are largely unknown because most of those studies were conducted in Europe and North America. In 2016 and from 2021 to 2022, we deployed satellite tracking devices on 22 and 10 mute swans wintering at the Ili River, Xinjiang of Western China, and summering at Ulansuhai Lake, Inner Mongolia of Eastern China, to determine their migration routes. Eight environmental factors, namely, human population density, the shortest distance to the nearest transportation route, elevation, aspect, slope, air temperature, wind speed and gross primary productivity (GPP), were used to analyse the environmental differences at the stopover sites of swan populations between Eastern and Western China. Ebinur and Ulungur Lakes in Xinjiang of Western China and Kapchagay Reservoir and Sasykkol and Alakol Lakes in Eastern Kazakhstan were the summering sites for the Western Chinese swan population; for the Eastern Chinese swan population, in addition to the Yellow River Delta being identified as a wintering site, the Hongze Lake Region of Jiangsu and Danaoban Lake of Inner Mongolia in China were also identified for the first time as wintering and summering sites, respectively. We also found that human population density and GPP were crucial determinants of stopover duration in the Eastern and Western Chinese swan populations both in spring and in autumn. Our findings provide basic data for future research on mute swans in East Asia and will contribute to conservation action plan development through current conservation status evaluations of important summering, wintering and stopover sites along the migration routes of mute swans.

Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress.

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

Environment pollution as a worldwide issue calls for high-performance adsorbent materials for effective removal and remediation. Nanocomposites have come to the force to remove pollutants due to their superior adsorption performances from nanosize effect, combination-versatility, and inheritance/transcendence of the parent constituents. Among them, molecular imprinting-based nanocomposites with tailor-made binding sites complementary to target molecules have drawn great research interests in environmental pollutants removal due to the outstanding recognition selectivity. Herein, the general fabrication and typical components of molecular imprinting-based nanocomposite adsorbents are summarized. Furthermore, synthesis strategies taken to improve the adsorption performances of nanocomposites are presented to provide a backdrop for future research.

Human metapneumovirus (hMPV) causes significant upper and lower respiratory disease in all age groups worldwide. However, there is no licensed drugs or vaccine available against hMPV. γ-Fagarine, an alkaloid isolated from the root of zanthoxylum, has been reported to be effective in the treatment of cancer, inflammatory diseases and antivirals. However, little is known about the inhibitory effect of γ-Fagarine against respiratory virus infection and the mechanism. In this study, we aim to investigate the effect of γ-Fagarine on hMPV infection and explore its underlying molecular mechanisms. Vero-E6 and 16HBE cells were used as cell models. Virus replication and microcosm character were explored in Vero-E6 cells. Then, the antiviral activities were investigated by quantitative real-time PCR (RT-qPCR), western blotting (WB), and indirect immunofluorescence assays (IFAs) in Vero-E6 and 16HBE. Potential mechanisms of γ-Fagarine related to HSPG and lysosome pH were assessed in 16HBE cells. Lastly, a virus-infected mouse model was established and antiviral assay in vivo was conducted. γ-Fagarine showed no toxicity toward Vero-E6 cells and 16HBE cells but demonstrated anti-hMPV activity. Virus titers of γ-Fagarine group were reduced to 33% and 45% of the hMPV groups, respectively. Besides, mechanistic studies revealed that γ-Fagarine could inhibit hMPV by dual mechanisms of direct restraining virus binding with HSPG and influencing lysosome pH. Furthermore, oral delivery of γ-Fagarine to hMPV-infected mice at a dosage of 25 mg/kg reduced the hMPV load in lung tissues. After γ-Fagarine treatment, pathological damage caused by viral infection was also ameliorated. These findings suggest that γ-Fagarine has antiviral effects in vitro and in vivo, which are associated with its ability to restrain virus binding with HSPG and influence lysosome pH, thus indicating that γ-Fagarine has the potential to serve as a candidate to fight against hMPV infection and other respiratory viruses such as influenza viruses and SARS-CoV-2.

2,6-dichloro-1,4-benzoquinone (DCBQ) has been identified as an emerging disinfection byproducts (DBPs) in drinking water and has the potential to induce neurodevelopmental toxicity. However, there is rarely a comprehensive toxicological evaluation of the neurodevelopmental toxicity of DCBQ. Here, neural differentiating SH-SY5Y cells were used as an in vitro model. Our results have found that DCBQ has decreased cell viability and neural differentiation, generated higher level of reactive oxygen species (ROS), increased the percentage of apoptosis and lowered the level of mitochondrial membrane potential, suggesting the neurodevelopmental toxicity of DCBQ. In addition, antioxidant N-acetyl-L-cysteine (NAC) could significantly attenuate these DCBQ-induced neurotoxic effects, supporting our hypothesis that the neurodevelopmental toxicity may be related with oxidative stress induced by DCBQ. We further demonstrated that DCBQ-induced neurodevelopmental toxicity could promote the mitochondrial apoptosis pathway and inhibit the prosurvival PI3K/AKT/mTOR pathway through inducing ROS, which ultimately inhibited cell proliferation and induced apoptosis in neural differentiating SH-SY5Y cells. These findings have provided novel insights into the risk of neurodevelopmental toxic effects associated with DCBQ exposure, emphasizing the importance of assessing the potential neurodevelopmental toxicity of DBPs.

Objective: This study aimed to assess the occurrence of chemotherapy-induced nausea and vomiting (CINV) in acute phase (24 h after chemotherapy) and delayed phase (2–5 days after chemotherapy) after standard antiemetic therapy and to explore the risk factors of CINV in the acute and delayed phases. Methods: This prospective and observational study analyzed the data of 400 breast cancer patients scheduled for chemotherapy in two hospitals. The self-report survey was developed to assess the occurrence of CINV and their associated factors. On day 2 and day 6 of chemotherapy, CINV was evaluated by the Multinational Association of Supportive Care in Cancer Antiemetic Tool (MAT). The incidence of acute and delayed CINV was expressed as frequency and percentage. Results: Among 400 patients, 29.8% and 23.5% experienced acute and delayed CINV, respectively. Logistic regression analysis showed that the risk factors associated with acute CINV included pain/insomnia, history of CINV, and highly emetogenic chemotherapy. The history of motion sickness (MS), history of CINV, number of chemotherapy cycles completed, and the incidence of acute CINV were significant risk factors for delayed CINV (all P < 0.05). Conclusions: The results of this study are helpful for nurses to identify high-risk patients with CINV, formulate effective treatment plans, and reduce the incidence of CINV.

There is a growing attention regarding the toxic effect of microplastics pollutants. However, comprehensive phenotyping- and omics-based strategies for the toxicity evaluation of microplastics on the host remain to be established. To this end, we designed an encompassing phenotyping and multi-omics analysis method to detect the molecular interference of nanopolystyrene (PS)-exposed mice. The exposure time was 28 days with 1000 μg/L PS. We found that PS induced microbial alteration and metabolic disorders, which was closely related to immune disturbances. In addition, the altered expression of some genes related to immune dysregulation was observed. Interestingly, Bifidobacterium breve M-16V (B. breve M-16V) significantly inhibited Th2 and Th17 lymphocyte subset. Simultaneously, B.breve M-16V may activate MyD88 expression and promote Th1-related cytokine IL-12 production. In addition, B. breve M-16V may partially restore the gut microbiota dysbiosis. In summary, we demonstrated that the combined phenotyping and omics-based profiling established a practical framework that allowed us to gain a deeper understanding of the maladaptive consequences of PS exposure. It can be utilized to evaluate the toxicity of other environmental microplastics pollutants. Meanwhile, we found that B. breve M-16V has certain anti-inflammatory and immunomodulatory functions through host-microbiome interactions.

As one of the most complete archaic human fossils, the Harbin cranium provides critical evidence for studying the diversification of the Homo genus and the origin of Homo sapiens. However, the unsystematic recovery of this cranium and a long and confused history since the discovery impede its accurate dating. Here, we carried out a series of geochemical analyses, including non-destructive X-ray fluorescence (XRF), rare earth elements (REE), and the Sr isotopes, to test the reported provenance of the Harbin cranium and get better stratigraphic constraints. The results show that the Harbin cranium has very similar XRF element distribution patterns, REE concentration patterns, and Sr isotopic compositions to those of the Middle Pleistocene-Holocene mammalian and human fossils recently recovered from the Harbin area. The sediments adhered in the nasal cavity of the Harbin cranium have a 87Sr/86Sr ratio of 0.711898, falling in the variation range measured in a core drilled near the Dongjiang Bridge, where the cranium was discovered during its reconstruction. The regional stratigraphic correlations indicate that the Harbin cranium was probably from the upper part of the Upper Huangshan Formation of the Harbin area, which has an optically stimulated luminescence dating constraint between 138 and 309 ka. U-series disequilibrium dating (n = 10) directly on the cranium suggests that the cranium is older than 146 ka. The multiple lines of evidence from our experiments consistently support the theory that the Harbin cranium is from the late Middle Pleistocene of the Harbin area. Our study also shows that geochemical approaches can provide reliable evidence for locating and dating unsystematically recovered human fossils, and potentially can be applied to other human fossils without clear provenance and stratigraphy records. Public summary: • Unsystematic recovery of the Harbin fossil cranium and a long history since the discovery impede its accurate dating • Geochemical analyses, including non-destructive X-ray fluorescence, rare earth elements, and the strontium isotopes, suggest that the fossil cranium was from a bed of lacustrine sediments aged between 138 and 309 thousand years ago in the Harbin region • Uranium-series disequilibrium dating directly on the cranium suggests that the cranium is older than 146 thousand years

It has recently become clear that several human lineages coexisted with Homo sapiens during the late Middle and Late Pleistocene. Here, we report an archaic human fossil that throws new light on debates concerning the diversification of the Homo genus and the origin of H. sapiens. The fossil was recovered in Harbin city in northeastern China, with a minimum uranium-series age of 146 ka. This cranium is one of the best preserved Middle Pleistocene human fossils. Its massive size, with a large cranial capacity (∼1,420 mL) falling in the range of modern humans, is combined with a mosaic of primitive and derived characters. It differs from all the other named Homo species by presenting a combination of features, such as long and low cranial vault, a wide and low face, large and almost square orbits, gently curved but massively developed supraorbital torus, flat and low cheekbones with a shallow canine fossa, and a shallow palate with thick alveolar bone supporting very large molars. The excellent preservation of the Harbin cranium advances our understanding of several less-complete late Middle Pleistocene fossils from China, which have been interpreted as local evolutionary intermediates between the earlier species Homo erectus and later H. sapiens. Phylogenetic analyses based on parsimony criteria and Bayesian tip-dating suggest that the Harbin cranium and some other Middle Pleistocene human fossils from China, such as those from Dali and Xiahe, form a third East Asian lineage, which is a part of the sister group of the H. sapiens lineage. Our analyses of such morphologically distinctive archaic human lineages from Asia, Europe, and Africa suggest that the diversification of the Homo genus may have had a much deeper timescale than previously presumed. Sympatric isolation of small populations combined with stochastic long-distance dispersals is the best fitting biogeographical model for interpreting the evolution of the Homo genus. Public summary: • More than 100,000 years ago, several human species coexisted in Asia, Europe, and Africa • A completely preserved fossil human cranium discovered in the Harbin area provides critical evidence for understanding the evolution of humans and the origin of our species • The Harbin cranium has a large cranial capacity (∼1,420 mL) falling in the range of modern humans, but is combined with a mosaic of primitive and derived characters • Our comprehensive phylogenetic analyses suggest that the Harbin cranium represents a new sister lineage for Homo sapiens • A multi-directional “shuttle dispersal model” is more likely to explain the complex phylogenetic connections among African and Eurasian Homo species/populations

The ‘stress-gradient hypothesis’ predicts increasing facilitative interactions with increasing environmental stress, but it remains unclear if the prevailing type of interaction (i.e. facilitative or competitive) between dominant and subordinate plant species occurring in harsh environments is dependent on the plant functional type. In addition, most plant-species removal experiments in grasslands are short-term (1–2 years), which may imprecisely reflect transient effects arising from methodological limitations. We conducted a dominant species removal experiment in a subalpine ecosystem, containing a mosaic of grass-dominated and shrub-dominated community patches, both of which are common in the subalpine zone of the Qinghai-Tibetan Plateau. We examined the direction and magnitude of the effects of three co-dominant grass and a dominant shrub species on subordinate species richness and biomass over a 6-year period. Removal of the dominant grass species alleviated their competitive pressure on subdominant grasses, which resulted in similar total and grass biomass detected in the final year of the study. By contrast, shrub removal showed no effects on its subordinate species biomass. Furthermore, neither the removal of the dominant shrubs nor the grasses altered their respective subordinate species richness. Thus, in subalpine ecosystems that experience harsh environmental conditions, our results showed that the direction of interactive effects of dominant plant species on subordinate species may be dependent on the plant functional type and are not necessarily facilitative. Furthermore, we showed that longer-term plant-removal experiment observations may be required to better determine the effects of species removal for this subalpine and other montane ecosystem(s).

To date, the treatment of immune-mediated kidney diseases has only marginally benefited from highly specific biological drugs that have demonstrated remarkable effects in many other diseases. What accounts for this disparity? In April 2016, the International Society of Nephrology held a Nexus meeting on Translational Immunology in Nephrology in Berlin, Germany, to identify and discuss hurdles that block the translational flow of target identification, and preclinical and clinical target validation in the domain of immune-mediated kidney disease. A broad panel of experts including basic scientists, translational researchers, clinical trialists, pharmaceutical industry drug developers, and representatives of the American and European regulatory authorities made recommendations on how to overcome such hurdles at all levels of the translational research process. The results of these discussions are presented here, which may serve as a roadmap for how to optimize the process of developing more innovative and effective drugs for patients with immune-mediated kidney diseases.