EphB2-dependent prefrontal cortex activation promotes long-range social approach and partner responsiveness.

Social behavior starts with dynamic approach prior to the final consummation. The flexible processes ensure mutual feedback across social brains to transmit signals. However, how the brain responds to the initial social stimuli precisely to elicit timed behaviors remains elusive. Here, by using real-time calcium recording, we identify the abnormalities of EphB2 mutant with autism-associated Q858X mutation in processing long-range approach and accurate activity of prefrontal cortex (dmPFC). The EphB2-dependent dmPFC activation precedes the behavioral onset and is actively associated with subsequent social action with the partner. Furthermore, we find that partner dmPFC activity is responsive coordinately to the approaching WT mouse rather than Q858X mutant mouse, and the social defects caused by the mutation are rescued by synchro-optogenetic activation in dmPFC of paired social partners. These results thus reveal that EphB2 sustains neuronal activation in the dmPFC that is essential for the proactive modulation of social approach to initial social interaction.

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids.

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Altered immune pathways in patients of temporal lobe epilepsy with and without hippocampal sclerosis.

Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS). We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models. Our findings established the first immune related genes and possible regulatory pathways in TLE-HS patients and animal models, which provided a novel insight into disease pathogenesis in both patients and animal models. The immune related SOX2-OT/miR-671-5p/SPP1 axis may be the potential therapeutic target for TLE-HS.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: We carried out a systematic review and meta-analysis to assess the safety and effectiveness of hepatic arterial infusion chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (uHCC). METHODS: Eligible studies were searched by MEDLINE, the Cochrane Library, Embase, and Web of Science from January 1995 to January 2022, investigating eligible literature comparing HAIC and TACE for patients with HCC. The main outcome measures included progression-free survival (PFS), overall survival (OS), adverse events (AEs), objective response rate (ORR), and diseases control rate (DCR). RESULTS: Eight literature and 1028 patients were enrolled in this meta-analysis. The pooled PFS, OS, ORR, and DCR were HR = 0.89 (95% CI, 0.81-0.98), HR = 0.84 (95% CI, 0.75-0.93), OR = 2.77 (95% CI, 2.01-3.80), and OR = 4.64 (95% CI, 2.40-8.99), respectively. The adverse events of HAIC were lower than TACE. CONCLUSION: Our meta-analysis revealed that HAIC can achieve a better effect and survival benefits than TACE in patients with uHCC.

[Pollution Characteristics and Source Apportionment of Typical and Emerging Per- and Polyfluoroalkylated Substances in Tuojiang River Basin].

Forty-eight surface water samples were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in order to study the pollution characteristics and source apportionment of per- and polyfluoroalkylated substances (PFASs) in the Tuojiang River. The results showed that ΣPFASs in the Tuojiang River ranged from 12.5-3789 ng·L-1, and perfluorooctanoic acid (PFOA) was the predominant PFAS, with a concentration of 9.97-3764 ng·L-1 (73.6%-99.8%), suggesting that legacy PFASs were still the dominant PFASs in the Tuojiang River. The most frequently detected emerging PFASs was 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B), with a detection frequency of 100%, suggesting the wide use of F-53B in the Tuojiang River. Sodium 1H, 1H, 2H, 2H-perfluorooctane sulfonate (6:2 FTS) displayed the highest concentration among all emerging PFASs[nd-27.3 ng·L-1, mean:(9.12±7.70) ng·L-1], and the concentrations were at the higher levels compared to those in other rivers around the world. In addition, ΣPFASs showed the highest concentrations of ΣPFASs at the fluorochemical manufacturing park (FMP), followed by those in the Luzhou section (in the lower reaches of the Tuojiang River), indicating that the emission of FMP and human daily production activities were the main influencing factors of PFASs pollution in the Tuojiang River. The estimated flux of PFASs from the Tuojiang River to the Yangtze River was 353 kg·a-1, and PFOA displayed the greatest mass loading (348 kg·a-1), which could provide the basic data for controlling PFASs in the Tuojiang River.

[Degradation of Triphenyl Phosphate in Water by UV-driven Advanced Oxidation Processes].

As a type of emerging pollutant of concern, organophosphate esters (OPEs) have posed a moderate risk to the remote Antarctic waters. Triphenyl phosphate (TPHP) is a common type of OPEs in water, which has been proven to have toxic effects, bioaccumulation, and amplification effects and pose a great threat to the environment and human health. Fourier transform infrared spectroscopy (FT-IR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to investigate the degradation process of TPHP in three advanced oxidation processes (UV-AOPs), including ultraviolet-hydrogen peroxide (UV-H2O2), ultraviolet-titanium dioxide (UV-TiO2), and ultraviolet-persulfate (UV-PS) systems. This was the first instance of using FT-IR for the online observation of the change in infrared characteristic peaks in the degradation process of TPHP, and its degradation reaction kinetics, photodegradation products, and degradation pathways were analyzed. The results showed that TPHP could be effectively degraded under UV-H2O2, UV-TiO2, and UV-PS systems, and the photodegradation half-lives were 74, 150, and 89 min, respectively. The UV-H2O2 system had the best degradation effect on TPHP. Additionally, the degradation reactions of TPHP in three systems conformed to the first-order kinetics. When the concentration of H2O2 was 0-0.097 mol·L-1, the increase in H2O2 concentration promoted the degradation of TPHP, and when the concentration of TiO2 was 0-0.013 mol·L-1, the increase in TiO2 concentration promoted the degradation of TPHP. The photodegradation pathway of TPHP mainly included the P-O-C bond breaking, the C-H bond cleavage of the benzene ring structure and the hydrolysis reaction of TPHP. The UV-H2O2 system was used to degrade OPEs in the environmental water of Chengdu, and it was found that the removal rate of TPHP was 66% when the water samples of the park landscape water were degraded for 60 min.

Unexplained septic shock after colonoscopy with polyethylene glycol preparation in a young adult: A case report.

BACKGROUND: Colonoscopy has become a routine physical examination as people's health awareness has increased. Polyethylene glycol (PEG) is greatly used in bowel preparation before colonoscopy due to its price and safety advantages. Septic shock after colonoscopy with PEG preparation is extremely rare, with only very few cases in critically ill patients. Herein, we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation. CASE SUMMARY: A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years. The male's previous physical examination showed no abnormal indicators, and colonoscopy results were normal; however, he exhibited septic shock and markedly elevated white blood cell, C-reactive protein, and procalcitonin levels on the second day after colonoscopy. Immediate resuscitation and intensive care with appropriate antibiotics improved his condition. However, the blood and stool cultures did not detect the pathogen. CONCLUSION: Septic shock after colonoscopy is rare, especially in young adults. The authors considered the possibility of opportunistic infections after PEG bowel preparation, and clinicians should monitor patients for the possibility of such complications.

Allelic diversity and forensic estimations of the Beijing Hans: Comparative data on sequence-based and length-based STRs.

Short tandem repeat (STR) profiling is routinely used in forensic genetics. At present, STR analysis is mainly performed by capillary electrophoresis (CE). However, due to limitations associated with the CE method, STR genotyping has been limited to length polymorphisms only. Because next generation sequencing (NGS) is capable of providing full resolution STR data at the sequence variation level, the individual identification capability of forensic STR loci could be significantly improved. Here we present sequence-based STR data for the Beijing Han population in which 291 individuals were screened for 23 commonly used forensic STRs using the SeqTypeR24 CASE kit on an Ion PGM platform. In total, 234 length-based alleles and 356 sequence-based alleles, which included 22 novel core repeat sequences, were observed. The sequence-based matching probability and power of discrimination were superior to the length-based numbers for 16 loci bearing micro-variant alleles. Combined matching probability reached 8.2 × 10-29 for 23 STR loci at the sequence level. This was two orders of magnitude higher than the parameters at length level and provides a data base for sequence-based STR casework applications.

Mitochondrial genomes uncover the maternal history of the Pamir populations.

The Pamirs, among the world's highest mountains in Central Asia, are one of homelands with the most extreme high altitude for several ethnic groups. The settlement history of modern humans on the Pamirs remains still opaque. Herein, we have sequenced the mitochondrial DNA (mtDNA) genomes of 382 individuals belonging to eight populations from the Pamirs and the surrounding lowlands in Central Asia. We construct the Central Asian (including both highlanders and lowlanders) mtDNA haplogroup tree at the highest resolution. All the matrilineal components are assigned into the defined mtDNA haplogroups in East and West Eurasians. No basal lineages that directly emanate from the Eurasian founder macrohaplogroups M, N, and R are found. Our data support the origin of Central Asian being the result of East-West Eurasian admixture. The coalescence ages for more than 93% mtDNA lineages in Central Asians are dated after the last glacial maximum (LGM). The post-LGM and/or later dispersals/admixtures play dominant roles in shaping the maternal gene pool of Central Asians. More importantly, our analyses reveal the mtDNA heterogeneity in the Pamir highlanders, not only between the Turkic Kyrgyz and the Indo-European Tajik groups, but also among three highland Tajiks. No evidence supports positive selection or relaxation of selective constraints in the mtDNAs of highlanders as compared to that of lowlanders. Our results suggest a complex history for the peopling of Pamirs by multiple waves of migrations from various genetic resources during different time scales.

A cryptic mitochondrial DNA link between North European and West African dogs.

Domestic dogs have an ancient origin and a long history in Africa. Nevertheless, the timing and sources of their introduction into Africa remain enigmatic. Herein, we analyse variation in mitochondrial DNA (mtDNA) D-loop sequences from 345 Nigerian and 37 Kenyan village dogs plus 1530 published sequences of dogs from other parts of Africa, Europe and West Asia. All Kenyan dogs can be assigned to one of three haplogroups (matrilines; clades): A, B, and C, while Nigerian dogs can be assigned to one of four haplogroups A, B, C, and D. None of the African dogs exhibits a matrilineal contribution from the African wolf (Canis lupus lupaster). The genetic signal of a recent demographic expansion is detected in Nigerian dogs from West Africa. The analyses of mitochondrial genomes reveal a maternal genetic link between modern West African and North European dogs indicated by sub-haplogroup D1 (but not the entire haplogroup D) coalescing around 12,000 years ago. Incorporating molecular anthropological evidence, we propose that sub-haplogroup D1 in West African dogs could be traced back to the late-glacial dispersals, potentially associated with human hunter-gatherer migration from southwestern Europe.

EMPOP-quality mtDNA control region sequences from Kashmiri of Azad Jammu & Kashmir, Pakistan.

The mitochondrial DNA (mtDNA) control region (nucleotide position 16024-576) sequences were generated through Sanger sequencing method for 317 self-identified Kashmiris from all districts of Azad Jammu & Kashmir Pakistan. The population sample set showed a total of 251 haplotypes, with a relatively high haplotype diversity (0.9977) and a low random match probability (0.54%). The containing matrilineal lineages belonging to three different phylogeographic origins of Western Eurasian (48.9%), South Asian (47.0%) and East Asian (4.1%). The present study was compared to previous data from Pakistan and other worldwide populations (Central Asia, Western Asia, and East & Southeast Asia). The dataset is made available through EMPOP under accession number EMP00679 and will serve as an mtDNA reference database in forensic casework in Pakistan.