Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with the progression of gastroesophageal cancer.

BACKGROUND: Previous metabolic studies in upper digestive cancer have mostly been limited to cross-sectional study designs, which hinders the ability to effectively predict outcomes in the early stage of cancer. This study aims to identify key metabolites and metabolic pathways associated with the multistage progression of epithelial cancer and to explore their predictive value for gastroesophageal cancer (GEC) formation and for the early screening of esophageal squamous cell carcinoma (ESCC). METHODS: A case-cohort study within the 7-year prospective Esophageal Cancer Screening Cohort of Shandong Province included 77 GEC cases and 77 sub-cohort individuals. Untargeted metabolic analysis was performed in serum samples. Metabolites, with FDR q value < 0.05 and variable importance in projection (VIP) > 1, were selected as differential metabolites to predict GEC formation using Random Forest (RF) models. Subsequently, we evaluated the predictive performance of these differential metabolites for the early screening of ESCC. RESULTS: We found a distinct metabolic profile alteration in GEC cases compared to the sub-cohort, and identified eight differential metabolites. Pathway analyses showed dysregulation in D-glutamine and D-glutamate metabolism, nitrogen metabolism, primary bile acid biosynthesis, and steroid hormone biosynthesis in GEC patients. A panel of eight differential metabolites showed good predictive performance for GEC formation, with an area under the receiver operating characteristic curve (AUC) of 0.893 (95% CI = 0.816-0.951). Furthermore, four of the GEC pathological progression-related metabolites were validated in the early screening of ESCC, with an AUC of 0.761 (95% CI = 0.716-0.805). CONCLUSIONS: These findings indicated a panel of metabolites might be an alternative approach to predict GEC formation, and therefore have the potential to mitigate the risk of cancer progression at the early stage of GEC.

Does China's Pilot Carbon Market Cause Carbon Leakage? New Evidence from the Chemical, Building Material, and Metal Industries.

The carbon market is an effective market for reducing greenhouse gas emissions; however, the existence of carbon leakage affects the emissions reduction effect of the carbon market. Using the multiregional input-output (MRIO) model and the difference-in-differences (DID) methodology, this study examined whether the chemical, building materials, or metals industries in China's pilot carbon market have caused carbon leakage, the extent of the carbon leakage, and the areas to which the industries with carbon leakage have transferred their carbon emissions. The results showed that the pilot carbon market caused carbon leakage in the chemical, building materials, and metal industries. The building materials industry had the most serious carbon leakage, followed by the chemical industry, and the metal industry was the weakest. In addition, regardless of the industry, most of the areas affected by carbon leakage were concentrated in regions with relatively backward economic development and weak in-place environmental regulations, such as in the central and western regions. Compared with the other pilot areas, Guangdong was the area most likely to be affected by carbon leakage from other pilot areas. This study provides new evidence for the existence of carbon leakage in China's pilot carbon market from an industrial perspective.

Stereodivergent Synthesis of Biologically Active Spironucleoside Scaffolds via Catalytic Cyclopropanation of 4-exo-Methylene Furanosides.

Cyclopropane fusion of the only rotatable carbon-carbon bond in furanosyl nucleosides (i.e., exocyclic 4'-5') is a powerful design strategy to arrive at conformationally constrained analogues. Herein, we report a direct stereodivergent route toward the synthesis of the four possible configurations of 4-spirocyclopropane furanoses, which have been transformed into the corresponding 4'-spirocyclic adenosine analogues. The latter showed differential inhibition of the protein methyltransferase PRMT5-MEP50 complex, with one analogue inhibiting more effectively than adenosine itself, demonstrating the utility of rationally probing 4'-5' side chain orientations.

Regio- and Stereoselective Synthesis of C-4' Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues.

Novel C-4',C-5' cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4'-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Alternatively, an unusual stereoselective ionic [2 + 2] cycloaddition using methyl propiolate promoted by methylaluminoxane gave a complementary, more direct approach to such ribofuranoses. Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.

Ancient Mitochondrial Genomes Reveal Extensive Genetic Influence of the Steppe Pastoralists in Western Xinjiang.

The population prehistory of Xinjiang has been a hot topic among geneticists, linguists, and archaeologists. Current ancient DNA studies in Xinjiang exclusively suggest an admixture model for the populations in Xinjiang since the early Bronze Age. However, almost all of these studies focused on the northern and eastern parts of Xinjiang; the prehistoric demographic processes that occurred in western Xinjiang have been seldomly reported. By analyzing complete mitochondrial sequences from the Xiabandi (XBD) cemetery (3,500-3,300 BP), the up-to-date earliest cemetery excavated in western Xinjiang, we show that all the XBD mitochondrial sequences fall within two different West Eurasian mitochondrial DNA (mtDNA) pools, indicating that the migrants into western Xinjiang from west Eurasians were a consequence of the early expansion of the middle and late Bronze Age steppe pastoralists (Steppe_MLBA), admixed with the indigenous populations from Central Asia. Our study provides genetic links for an early existence of the Indo-Iranian language in southwestern Xinjiang and suggests that the existence of Andronovo culture in western Xinjiang involved not only the dispersal of ideas but also population movement.

A Contact-Sliding-Triboelectrification-Driven Dynamic Optical Transmittance Modulator for Self-Powered Information Covering and Selective Visualization.

Triboelectrification-enabled self-powered flexible electronic/optical systems have aroused a new surge of interest in recent years. All-in-one integration of such a system, which could significantly improve its adaptability, operability, and portability, still remains a challenge due to the absence of suitable architectures and integration schemes. Herein, a previously reported self-powered optical switch (OS) is thoroughly remolded and upgraded to a fully integrated contact-sliding-triboelectrification-driven dynamic optical transmittance modulator (OTM). The OTM is constructed with a multilayered structure, comprising a transparent triboelectrification top layer, a SiO2 -spaced polymer dispersed liquid crystal (PDLC) intermediate layer, and a flexible transparent conductive substrate. The working mechanism is that an alternating electric field can be induced once contact-sliding occurs upon the OTM, rendering the PDLC layer immediately switching its initial translucent state to an instantaneous transparent state. As such, a decent dimming range with the relative transmitted light intensity from 0.17 to 0.72 can be achieved at low mechanical thresholds of contact pressure (≈20 kPa) and sliding velocity (≈0.3 m s-1 ). Moreover, for practical applications, demonstrations of information covering and selective visualization are successfully implemented without any extra optical elements nor external power supplies, explicitly showing great potential for the OTM in various self-powered optical interactive applications.

Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders.

BACKGROUND/AIMS: To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. METHODS: Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). RESULTS: Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett's esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES ( P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). CONCLUSIONS: Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.

A Cut-and-Weld Process to 3D Architectures from Multiresponsive Crosslinked Liquid Crystalline Polymers.

Crosslinked liquid crystalline polymers (CLCPs) have garnered extensive attention in recent years for their significant values in the design of light-driven soft actuators. However, poor processabilities due to the insoluble and infusible crosslinked networks prevent their practical applications severely. In this study, a weldable azobenzene-containing CLCP is designed with photo- and humidity-responsive actuations, which enables a cut-and-weld process to 3D CLCP architectures. The tensile properties and stability are almost unchanged after welding, much better than those of the films pasted by common adhesive tapes. Meanwhile, the mechanisms of the welding process are clarified on the base of surface hydrogen bonding and further crosslinking. By taking advantage of the cut-and-weld process, a 3D "claw" integrated into a robotic arm is realized for grabbing millimeter-scale objects by remote control. This work enhances significantly not only the processability of CLCP films but also the utilization of leftover pieces, which provides an efficient approach to create functional 3D structures from film precursors for the potential application in the smart materials.

New-Onset Diabetes After Renal Transplantation (NODAT): Is It a Risk Factor for Renal Cell Carcinoma or Renal Failure?

BACKGROUND Diabetes mellitus (DM) is a risk factor for renal failure and possibly for renal cell carcinoma (RCC). Post-transplantation DM occurs frequently after solid organ transplantation. We investigated whether new-onset diabetes after renal transplantation (NODAT) is a risk factor for RCC or renal failure. MATERIAL AND METHODS Data of 96,699 discharged patients with and without NODAT were extracted from the 2005-2014 Nationwide Inpatient Sample (NIS) database, after excluding patients with DM diagnosed at least 1 year prior to renal transplantation. Main outcomes were RCC diagnosis less than 1-year post-transplantation, RCC stage, and renal failure. Univariate and multivariate regression analyses were performed to identify demographic and clinical factors associated with post-transplantation RCC or renal failure. RESULTS Significant differences were found in age and race between patients with and without NODAT (both P<0.001). The renal failure rate was 0.8% (n=1) in NODAT patients and 0.3% (n=314) in those without NODAT. Older age (OR, 1.030; 95% CI: 1.023 to 1.036), male (OR, 1.872; 95% CI: 1.409 to 2.486), Black (OR, 2.199; 95% CI: 1.574 to 3.071) and hospitalization in urban teaching hospitals were associated with increased risk of RCC. CONCLUSIONS Analysis of over 90,000 NIS hospitalizations with diagnosis-coded kidney transplantation suggested that NODAT may not be an independent risk factor for RCC and renal failure.

Light-Triggered Reversible Slimming of Azobenzene-Containing Wormlike Nanoparticles Synthesized by Polymerization-Induced Self-Assembly for Nanofiltration Switches.

Photoresponsive wormlike block copolymer nanoparticles (NPs) have potential applications in versatile fields, but their preparation suffers from narrow worm phase region and tedious approaches. In this work, azobenzene-containing wormlike NPs based on poly(methylacrylic acid)-b-poly(4-((4-butylphenyl)diazenyl)phenyl methacrylate) are prepared via polymerization-induced self-assembly at high solids concentration in ethanol. The pure wormlike NPs occupy a remarkably broad region in the morphological phase diagram because of the rigid nature of the core-forming block. These wormlike NPs expand resulting from trans-cis transformation upon UV irradiation, and slim near to the original state via visible light irradiation. The diameter and its variation amplitude of worms increase with the chain length of core-forming block. Moreover, a nanofiltration switch for rhodamine B is assembled to illustrate one of its potential applications by remote trigger using light.

Liquid crystalline moiety-assisted perpendicular orientation of cylindrical domains within P4VP-b-PMA(Az) films with high aspect ratio.

Block copolymer (BCP) films with perpendicularly aligned cylindrical domains of high aspect ratio have important applications in diverse fields. However, an aspect ratio of the cylinders as high as 200 has rarely been reported so far. Here we demonstrate an efficient route to the formation of normally aligned P4VP cylinders with high aspect ratio surrounded by a matrix of azobenzene-containing block (PMA(Az)) via hierarchical self-assembly. A crisscross structure, consisting of parallelly aligned liquid crystalline (LC) layers and normally aligned self-assembly domains, is expected to assist the formation of well-defined nanostructures. The LC layers in the cylindrical films self-assemble to form smectic phase after solvent annealing, as confirmed by WAXD and UV-vis spectra. We found that the aspect ratio of the vertical P4VP cylinders is up to 200 and the film thickness reaches 6 µm. P4VP is a functional polymer, making this P4VP-b-PMA(Az) film more suitable for advanced filters, multi-nanochannels, nanolithography, and high-density storage media, etc.

Fully Rollable Lead-Free Poly(vinylidene fluoride)-Niobate-Based Nanogenerator with Ultra-Flexible Nano-Network Electrodes.

A fully rollable nanocomposite-based nanogenerator (NCG) is developed by integrating a lead-free piezoelectric hybrid layer with a type of nanofiber-supported silver nanowire (AgNW) network as electrodes. The thin-film nanocomposite is composed of electroactive polyvinylidene fluoride (PVDF) polymer matrix and compositionally modified potassium sodium niobate-based nanoparticles (NPs) with a high piezoelectric coefficient ( d33) of 53 pm/V, which is revealed by the piezoresponse force microscopy measurements. Under periodical agitation at a compressive force of 50 N and 1 Hz, the NCG can steadily render high electric output up to an open-circuit voltage of 18 V and a short-circuit current of 2.6 µA. Of particular importance is the decent rollability of the NCG, as indicated by the negligible decay in the electric output after it being repeatedly rolled around a gel pen for 200 cycles. Besides, the biocompatible NCG can potentially be used to scavenge biomechanical energy from low-frequency human motions, as demonstrated by the scenarios of walking and elbow joint movement. These results rationally expand the feasibility of the developed NCG toward applications in lightweight, diminutive, and multifunctional rollable or wearable electronic devices.

The genome of an ancient Rouran individual reveals an important paternal lineage in the Donghu population.

OBJECTIVES: Following the Xiongnu and Xianbei, the Rouran Khaganate (Rouran) was the third great nomadic tribe on the Mongolian Steppe. However, few human remains from this tribe are available for archaeologists and geneticists to study, as traces of the tombs of these nomadic people have rarely been found. In 2014, the IA-M1 remains (TL1) at the Khermen Tal site from the Rouran period were found by a Sino-Mongolian joint archaeological team in Mongolia, providing precious material for research into the genetic imprint of the Rouran. MATERIALS AND METHODS: The mtDNA hypervariable sequence I (HVS-I) and Y-chromosome SNPs were analyzed, and capture of the paternal non-recombining region of the Y chromosome (NRY) and whole-genome shotgun sequencing of TL1 were performed. The materials from three sites representing the three ancient nationalities (Donghu, Xianbei, and Shiwei) were selected for comparison with the TL1 individual. RESULTS: The mitochondrial haplotype of the TL1 individual was D4b1a2a1. The Y-chromosome haplotype was C2b1a1b/F3830 (ISOGG 2015), which was the same as that of the other two ancient male nomadic samples (ZHS5 and GG3) related to the Xianbei and Shiwei, which were also detected as F3889; this haplotype was reported to be downstream of F3830 by Wei et al. (). DISCUSSION: We conclude that F3889 downstream of F3830 is an important paternal lineage of the ancient Donghu nomads. The Donghu-Xianbei branch is expected to have made an important paternal genetic contribution to Rouran. This component of gene flow ultimately entered the gene pool of modern Mongolic- and Manchu-speaking populations.

The Y-chromosome haplogroup C3*-F3918, likely attributed to the Mongol Empire, can be traced to a 2500-year-old nomadic group.

The Mongol Empire had a significant role in shaping the landscape of modern populations. Many populations living in Eurasia may have been the product of population mixture between ancient Mongolians and natives following the expansion of Mongol Empire. Geneticists have found that most of these populations carried the Y-haplogroup C3* (C-M217). To trace the history of haplogroup (Hg) C3* and to further understand the origin and development of Mongolians, ancient human remains from the Jinggouzi, Chenwugou and Gangga archaeological sites, which belonged to the Donghu, Xianbei and Shiwei, respectively, were analysed. Our results show that nine of the eleven males of the Gangga site, two of the eight males of Chengwugou site and all of the twelve males of Jinggouzi site were found to have mutations at M130 (Hg C), M217 (Hg C3), L1373 (C2b, ISOGG2015), with the absence of mutations at M93 (Hg C3a), P39 (Hg C3b), M48 (Hg C3c), M407 (Hg C3d) and P62 (Hg C3f). These samples were attributed to the Y-chromosome Hg C3* (Hg C2b, ISOGG2015), and most of them were further typed as Hg C2b1a based on the mutation at F3918. Finally, we inferred that the Y-chromosome Hg C3*-F3918 can trace its origins to the Donghu ancient nomadic group.

Formation of Anisotropic Liquid Crystalline Nanoparticles via Polymerization-Induced Hierarchical Self-Assembly.

Polymeric nanoparticles (NPs) containing liquid crystalline (LC) mesogens with tunable anisotropic morphologies have applications in various fields, but their preparation typically suffers from tedious and low-throughput approaches. Here we present an efficient route to the preparation of anisotropic morphologies of azobenzene-containing block copolymers (BCPs) at high solids content via a polymerization-induced hierarchical self-assembly in ethanol. Various anisotropic NPs, including cuboids, short belts, lamellae, and ellipsoidal vesicles, have been obtained in a remarkably broad range of BCP compositions. The NPs exhibit a smectic phase with ordered stripes when observed under TEM. This internal LC ordering plays a significant role on the formation of these intriguing anisotropic morphologies. Morphological transitions from anisotropic to isotropic spheres can be obtained upon UV illumination due to the photoresponsive properties of the azobenzene mesogens. This work significantly expands the scope of accessible morphologies in PISA and suggests that the under explored LC BCPs may have an impactful role in the PISA field.

Nanoporous Films with Sub-10 nm in Pore Size from Acid-Cleavable Block Copolymers.

Nanoporous thin films with pore size of sub-10 nm are fabricated using an acid-cleavable block copolymer (BCP), a benzoic imine junction between poly(ethylene oxide) (PEO) and poly(methacrylate) (PMAAz) bearing an azobenzene side chain (denoted as PEO-bei-PMAAz) as the precursor. After a thermal annealing, the block copolymers are self-assembled to form highly ordered PEO cylinders within a PMAAz matrix normal to the film, even in the case of low BCP molecular weight due to the existing of the liquid crystalline (LC) azobenzene rigid segment. Thus, PMAAz thin films with pore size of ≈7 nm and density of ≈1012 cm-2 are obtained after removal of the PEO minor phase by breaking the benzoic imine junction under mild acidic conditions. This work enriches the nanoporous polymer films from BCP precursors and introduces the LC property as a functionality which can further enhance the mechanical properties of the films and broaden their applications.

[Establishment of a penile transplantation model in beagle dogs].

OBJECTIVE: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS: The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.

Genetic diversity of two Neolithic populations provides evidence of farming expansions in North China.

The West Liao River Valley and the Yellow River Valley are recognized Neolithic farming centers in North China. The population dynamics between these two centers have significantly contributed to the present-day genetic patterns and the agricultural advances of North China. To understand the Neolithic farming expansions between the West Liao River Valley and the Yellow River Valley, we analyzed mitochondrial DNA (mtDNA) and the Y chromosome of 48 individuals from two archeological sites, Jiangjialiang (>3000 BC) and Sanguan (~1500 BC). These two sites are situated between the two farming centers and experienced a subsistence shift from hunting to farming. We did not find a significant difference in the mtDNA, but their genetic variations in the Y chromosome were different. Individuals from the Jiangjialiang belonged to two Y haplogroups, N1 (not N1a or N1c) and N1c. The individuals from the Sanguan are Y haplogroup O3. Two stages of migration are supported. Populations from the West Liao River Valley spread south at about 3000 BC, and a second northward expansion from the Yellow River Valley occurred later (3000-1500 BC).