bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure
Authors: Yan Wanhao , Lin Xiao , Ying Yiqian , Li Jun , Fan Zhipeng
Published: January 2023

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the “m6A site methylation stoichiometry” of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3′-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.
MANF ameliorates DSS-induced mouse colitis via restricting Ly6ChiCX3CR1int macrophage transformation and suppressing CHOP-BATF2 signaling pathway
Authors: Yang Lin , Shen Wen-wen , Shao Wei , Zhao Qing , Pang Gao-zong , Yang Yi , Tao Xiao-fang , Zhang Wei-ping , Mei Qiong , Shen Yu-xian
Published: January 2023

Mesencephalic astrocyte-derived neurotrophic factor (MANF), an endoplasmic reticulum stress-inducible secreting protein, has evolutionarily conserved immune-regulatory function that contributes to the negative regulation of inflammation in macrophages. In this study, we investigated the profiles of MANF in the macrophages of the patients with active inflammatory bowel disease (IBD) and the mice with experimental colitis, which was induced in both myeloid cell-specific MANF knockout mice and wild-type mice by 3% dextran sodium sulfate (DSS) for 7 days. We found that MANF expression was significantly increased in intestinal macrophages from both the mice with experimental colitis and patients with active IBD. DSS-induced colitis was exacerbated in myeloid cell-specific MANF knockout mice. Injection of recombinant human MANF (rhMANF, 10 mg·kg–1·d–1, i.v.) from D4 to D6 significantly ameliorated experimental colitis in DSS-treated mice. More importantly, MANF deficiency in myeloid cells resulted in a dramatic increase in the number of Ly6ChiCX3CRintproinflammatory macrophages in colon lamina propria of DSS-treated mice, and the proinflammatory cytokines and chemokines were upregulated as well. Meanwhile, we demonstrated that MANF attenuated Th17-mediated immunopathology by inhibiting BATF2-mediated innate immune response and downregulating CXCL9, CXCL10, CXCL11 and IL-12p40; MANF functioned as a negative regulator in inflammatory macrophages via inhibiting CHOP-BATF2 signaling pathway, thereby protecting against DSS-induced mouse colitis. These results suggest that MANF ameliorates colon injury by negatively regulating inflammatory macrophage transformation, which shed light on a potential therapeutic target for IBD.
A pooled analysis of outcomes according to cytogenetic abnormalities in patients receiving ixazomib- vs placebo-based therapy for multiple myeloma
Authors: Chng Wee-Joo , Lonial Sagar , Morgan Gareth J. , Iida Shinsuke , Moreau Philippe , Kumar Shaji K. , Twumasi-Ankrah Philip , Villarreal Miguel , Dash Ajeeta B. , Vorog Alexander , Zhang Xiaoquan , Suryanarayan Kaveri , Labotka Richard , Dimopoulos Meletios A. , Rajkumar S. Vincent
Published: January 2023

Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs placebo-based therapy for high-risk patients was 0.74 (95% confidence interval [CI]: 0.59–0.93; median PFS [mPFS] 17.8 vs 13.2 months), and 0.70 (95% CI: 0.62–0.80; mPFS 26.3 vs 17.6 months) for complementary standard-risk patients. The HR for expanded high-risk patients was 0.75 (95% CI: 0.64–0.87; mPFS 18.1 vs 14.1 months), and 0.71 (95% CI: 0.59–0.85; mPFS 36.1 vs 21.4 months) for complementary standard-risk patients. The HR for PFS with ixazomib- vs placebo-based therapy was 0.68 in patients with t(4;14) (95% CI: 0.48–0.96; mPFS 22.4 vs 13.2 months), and 0.77 for patients with amp1q21 (95% CI: 0.63–0.93; mPFS 18.8 vs 14.5 months). A PFS benefit was demonstrated with ixazomib- vs placebo-based therapy regardless of cytogenetic status, with greatest benefit observed in patients with t(4;14) and amp1q21.
NCBP2 and TFRC are novel prognostic biomarkers in oral squamous cell carcinoma
Authors: Arora Rahul , Haynes Logan , Kumar Mehul , McNeil Reid , Ashkani Jahanshah , Nakoneshny Steven C. , Matthews T. Wayne , Chandarana Shamir , Hart Robert D. , Jones Steven J. M. , Dort Joseph C. , Itani Doha , Chanda Ayan , Bose Pinaki
Published: January 2023

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC.
CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export
Authors: Yu Xiaopeng , Tong Huanjun , Chen Jialu , Tang Chenwei , Wang Shuqing , Si Yu , Wang Shouhua , Tang Zhaohui
Published: January 2023

The carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well-established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression, such as circRNAs, regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism-related circRNA, circMBOAT2 (hsa_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. CircMBOAT2 knockdown inhibits the growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protects PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.
Microglia and meningeal macrophages depletion delays the onset of experimental autoimmune encephalomyelitis
Authors: Montilla Alejandro , Zabala Alazne , Er-Lukowiak Marco , Rissiek Björn , Magnus Tim , Rodriguez-Iglesias Noelia , Sierra Amanda , Matute Carlos , Domercq María
Published: January 2023

In multiple sclerosis and the experimental autoimmune encephalomyelitis (EAE) model, both resident microglia and infiltrating macrophages contribute to demyelination as well as spontaneous remyelination. Nevertheless, the specific roles of microglia versus macrophages are unknown. We investigated the influence of microglia in EAE using the colony stimulating factor 1 receptor (CSF-1R) inhibitor, PLX5622, to deplete microglial population andCcr2RFP/+fmsEGFP/+mice, to distinguish blood-derived macrophages from microglia. PLX5622 treatment depleted microglia and meningeal macrophages, and provoked a massive infiltration of CCR2+macrophages into demyelinating lesions and spinal cord parenchyma, albeit it did not alter EAE chronic phase. In contrast, microglia and meningeal macrophages depletion reduced the expression of major histocompatibility complex II and CD80 co-stimulatory molecule in dendritic cells, macrophages and microglia. In addition, it diminished T cell reactivation and proliferation in the spinal cord parenchyma, inducing a significant delay in EAE onset. Altogether, these data point to a specific role of CNS microglia and meningeal macrophages in antigen presentation and T cell reactivation at initial stages of EAE.
Hippo pathway dysregulation in gastric cancer: from Helicobacter pylori infection to tumor promotion and progression
Authors: Messina Beatrice , Lo Sardo Federica , Scalera Stefano , Memeo Lorenzo , Colarossi Cristina , Mare Marzia , Blandino Giovanni , Ciliberto Gennaro , Maugeri-Saccà Marcello , Bon Giulia
Published: January 2023

The Hippo pathway plays a critical role for balancing proliferation and differentiation, thus regulating tissue homeostasis. The pathway acts through a kinase cascade whose final effectors are the Yes-associated protein (YAP) and its paralog transcriptional co‑activator with PDZ‑binding motif (TAZ). In response to a variety of upstream signals, YAP and TAZ activate a transcriptional program that modulates cellular proliferation, tissue repair after injury, stem cell fate decision, and cytoskeletal reorganization. Hippo pathway signaling is often dysregulated in gastric cancer and in Helicobacter pylori-induced infection, suggesting a putative role of its deregulation since the early stages of the disease. In this review, we summarize the architecture and regulation of the Hippo pathway and discuss how its dysregulation fuels the onset and progression of gastric cancer. In this setting, we also focus on the crosstalk between Hippo and other established oncogenic signaling pathways. Lastly, we provide insights into the therapeutic approaches targeting aberrant YAP/TAZ activation and discuss the related clinical perspectives and challenges.
Genetic conversion of a split-drive into a full-drive element
Authors: Terradas Gerard , Bennett Jared B. , Li Zhiqian , Marshall John M. , Bier Ethan
Published: January 2023

The core components of CRISPR-based gene drives, Cas9 and guide RNA (gRNA), either can be linked within a self-contained single cassette (full gene-drive, fGD) or be provided in two separate elements (split gene-drive, sGD), the latter offering greater control options. We previously engineered split systems that could be converted genetically into autonomous full drives. Here, we examine such dual systems inserted at the spo11 locus that are recoded to restore gene function and thus organismic fertility. Despite minimal differences in transmission efficiency of the sGD or fGD drive elements in single generation crosses, the reconstituted spo11 fGD cassette surprisingly exhibits slower initial drive kinetics than the unlinked sGD element in multigenerational cage studies, but then eventually catches up to achieve a similar level of final introduction. These unexpected kinetic behaviors most likely reflect differing transient fitness costs associated with individuals co-inheriting Cas9 and gRNA transgenes during the drive process.
A specific G9a inhibitor unveils BGLT3 lncRNA as a universal mediator of chemically induced fetal globin gene expression
Authors: Takase Shohei , Hiroyama Takashi , Shirai Fumiyuki , Maemoto Yuki , Nakata Akiko , Arata Mayumi , Matsuoka Seiji , Sonoda Takeshi , Niwa Hideaki , Sato Shin , Umehara Takashi , Shirouzu Mikako , Nishigaya Yosuke , Sumiya Tatsunobu , Hashimoto Noriaki , Namie Ryosuke , Usui Masaya , Ohishi Tomokazu , Ohba Shun-ichi , Kawada Manabu , Hayashi Yoshihiro , Harada Hironori , Yamaguchi Tokio , Shinkai Yoichi , Nakamura Yukio , Yoshida Minoru , Ito Akihiro
Published: January 2023

Sickle cell disease (SCD) is a heritable disorder caused by β-globin gene mutations. Induction of fetal γ-globin is an established therapeutic strategy. Recently, epigenetic modulators, including G9a inhibitors, have been proposed as therapeutic agents. However, the molecular mechanisms whereby these small molecules reactivate γ-globin remain unclear. Here we report the development of a highly selective and non-genotoxic G9a inhibitor, RK-701. RK-701 treatment induces fetal globin expression both in human erythroid cells and in mice. Using RK-701, we find that BGLT3 long non-coding RNA plays an essential role in γ-globin induction. RK-701 selectively upregulates BGLT3 by inhibiting the recruitment of two major γ-globin repressors in complex with G9a onto the BGLT3 gene locus through CHD4, a component of the NuRD complex. Remarkably, BGLT3 is indispensable for γ-globin induction by not only RK-701 but also hydroxyurea and other inducers. The universal role of BGLT3 in γ-globin induction suggests its importance in SCD treatment.
Solid state ionics enabled ultra-sensitive detection of thermal trace with 0.001K resolution in deep sea
Authors: Zhang Yucheng , Ye Dekai , Li Mengxue , Zhang Xi , Di Chong-an , Wang Chao
Published: January 2023

The deep sea remains the largest uncharted territory on Earth because it’s eternally dark under high pressure and the saltwater is corrosive and conductive. The harsh environment poses great difficulties for the durability of the sensing method and the device. Sea creatures like sharks adopt an elegant way to detect objects by the tiny temperature differences in the seawater medium using their extremely thermo-sensitive thermoelectric sensory organ on the nose. Inspired by shark noses, we designed and developed an elastic, self-healable and extremely sensitive thermal sensor which can identify a temperature difference as low as 0.01 K with a resolution of 0.001 K. The sensor can work reliably in seawater or under a pressure of 110 MPa without any encapsulation. Using the integrated temperature sensor arrays, we have constructed a model of an effective deep water mapping and detection device.
Programmable frequency-bin quantum states in a nano-engineered silicon device
Authors: Clementi Marco , Sabattoli Federico Andrea , Borghi Massimo , Gianini Linda , Tagliavacche Noemi , El Dirani Houssein , Youssef Laurene , Bergamasco Nicola , Petit-Etienne Camille , Pargon Erwine , Sipe J. E. , Liscidini Marco , Sciancalepore Corrado , Galli Matteo , Bajoni Daniele
Published: January 2023

Photonic qubits should be controllable on-chip and noise-tolerant when transmitted over optical networks for practical applications. Furthermore, qubit sources should be programmable and have high brightness to be useful for quantum algorithms and grant resilience to losses. However, widespread encoding schemes only combine at most two of these properties. Here, we overcome this hurdle by demonstrating a programmable silicon nano-photonic chip generating frequency-bin entangled photons, an encoding scheme compatible with long-range transmission over optical links. The emitted quantum states can be manipulated using existing telecommunication components, including active devices that can be integrated in silicon photonics. As a demonstration, we show our chip can be programmed to generate the four computational basis states, and the four maximally-entangled Bell states, of a two-qubits system. Our device combines all the key properties of on-chip state reconfigurability and dense integration, while ensuring high brightness, fidelity, and purity.
Gas induced formation of inactive Li in rechargeable lithium metal batteries
Authors: Xiang Yuxuan , Tao Mingming , Chen Xiaoxuan , Shan Peizhao , Zhao Danhui , Wu Jue , Lin Min , Liu Xiangsi , He Huajin , Zhao Weimin , Hu Yonggang , Chen Junning , Wang Yuexing , Yang Yong
Published: January 2023

The formation of inactive lithium by side reactions with liquid electrolyte contributes to cell failure of lithium metal batteries. To inhibit the formation and growth of inactive lithium, further understanding of the formation mechanisms and composition of inactive lithium are needed. Here we study the impact of gas producing reactions on the formation of inactive lithium using ethylene carbonate as a case study. Ethylene carbonate is a common electrolyte component used with graphite-based anodes but is incompatible with Li metal anodes. Using mass spectrometry titrations combined with 13C and 2H isotopic labeling, we reveal that ethylene carbonate decomposition continuously releases ethylene gas, which further reacts with lithium metal to form the electrochemically inactive species LiH and Li2C2. In addition, phase-field simulations suggest the non-ionically conducting gaseous species could result in an uneven distribution of lithium ions, detrimentally enhancing the formation of dendrites and dead Li. By optimizing the electrolyte composition, we selectively suppress the formation of ethylene gas to limit the formation of LiH and Li2C2 for both Li metal and graphite-based anodes.
Pt nanoclusters on GaN nanowires for solar-asssisted seawater hydrogen evolution
Authors: Dong Wan Jae , Xiao Yixin , Yang Ke R. , Ye Zhengwei , Zhou Peng , Navid Ishtiaque Ahmed , Batista Victor S. , Mi Zetian
Published: January 2023

Seawater electrolysis provides a viable method to produce clean hydrogen fuel. To date, however, the realization of high performance photocathodes for seawater hydrogen evolution reaction has remained challenging. Here, we introduce n+-p Si photocathodes with dramatically improved activity and stability for hydrogen evolution reaction in seawater, modified by Pt nanoclusters anchored on GaN nanowires. We find that Pt-Ga sites at the Pt/GaN interface promote the dissociation of water molecules and spilling H* over to neighboring Pt atoms for efficient H2 production. Pt/GaN/Si photocathodes achieve a current density of −10 mA/cm2 at 0.15 and 0.39 V vs. RHE and high applied bias photon-to-current efficiency of 1.7% and 7.9% in seawater (pH = 8.2) and phosphate-buffered seawater (pH = 7.4), respectively. We further demonstrate a record-high photocurrent density of ~169 mA/cm2 under concentrated solar light (9 suns). Moreover, Pt/GaN/Si can continuously produce H2 even under dark conditions by simply switching the electrical contact. This work provides valuable guidelines to design an efficient, stable, and energy-saving electrode for H2 generation by seawater splitting.
Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial
Authors: van Beek Sten M. M. , Bruls Yvonne M. H. , Vanweert Froukje , Fealy Ciarán E. , Connell Niels J. , Schaart Gert , Moonen-Kornips Esther , Jörgensen Johanna A. , Vaz Frédéric M. , Smeets Ellen T. H. C. , Joris Peter J. , Gemmink Anne , Houtkooper Riekelt H. , Hesselink Matthijs K. C. , Bengtsson Tore , Havekes Bas , Schrauwen Patrick , Hoeks Joris
Published: January 2023

β2-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the β2-agonist clenbuterol (40 µg/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m2) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.gov-identifier: NCT03800290). Randomisation occurred by controlled randomisation and the final allocation sequence was seven (period 1: clenbuterol, period 2: placebo) to four (period 1: placebo, period 2: clenbuterol). The primary and secondary outcome were peripheral insulin-stimulated glucose disposal and skeletal muscle GLUT4 translocation, respectively. Primary analyses were performed on eleven participants. No serious adverse events were reported. The study was performed at Maastricht University, Maastricht, The Netherlands, between August 2019 and April 2021. Clenbuterol treatment improved peripheral insulin-stimulated glucose disposal by 13% (46.6 ± 3.5 versus 41.2 ± 2.7 µmol/kg/min, p = 0.032), whereas skeletal muscle GLUT4 translocation assessed in overnight fasted muscle biopsies remained unaffected. These results highlight the potential of β2-agonist treatment in improving skeletal muscle glucose uptake and underscore the therapeutic value of this pathway for the treatment of type 2 diabetes. However, given the well-known (cardiovascular) side-effects of systemic β2-agonist treatment, further exploration on the underlying mechanisms is needed to identify viable therapeutic targets.
2D conjugated microporous polyacetylenes synthesized via halogen-bond-assisted radical solid-phase polymerization for high-performance metal-ion absorbents
Authors: Le Hong Tho , Wang Chen-Gang , Goto Atsushi
Published: January 2023

The paper reports the first free-radical solid-phase polymerization (SPP) of acetylenes. Acetylene monomers were co-crystalized using halogen bonding, and the obtained cocrystals were polymerized. Notably, because of the alignment of acetylene monomers in the cocrystals, the adjacent C≡C groups were close enough to undergo radical polymerization effectively, enabling the radically low-reactive acetylene monomers to generate high-molecular-weight polyacetylenes that are unattainable in solution-phase radical polymerizations. Furthermore, the SPP of a crosslinkable diacetylene monomer yielded networked two-dimensional conjugated microporous polymers (2D CMPs), where 2D porous polyacetylene nanosheets were cumulated in layer-by-layer manners. Because of the porous structures, the obtained 2D CMPs worked as highly efficient and selective adsorbents of lithium (Li+) and boronium (B3+) ions, adsorbing up to 312 mg of Li+ (31.2 wt%) and 196 mg of B3+ (19.6 wt%) per 1 g of CMP. This Li+ adsorption capacity is the highest ever record in the area of Li+ adsorption.
Effectiveness of mRNA-1273 vaccination against SARS-CoV-2 omicron subvariants BA.1, BA.2, BA.2.12.1, BA.4, and BA.5
Authors: Tseng Hung Fu , Ackerson Bradley K. , Bruxvoort Katia J. , Sy Lina S. , Tubert Julia E. , Lee Gina S. , Ku Jennifer H. , Florea Ana , Luo Yi , Qiu Sijia , Choi Soon Kyu , Takhar Harpreet S. , Aragones Michael , Paila Yamuna D. , Chavers Scott , Talarico Carla A. , Qian Lei
Published: January 2023

Studies have reported reduced natural SARS-CoV-2 infection- and vaccine-induced neutralization against omicron BA.4/BA.5 compared with earlier omicron subvariants. This test-negative case–control study evaluates mRNA-1273 vaccine effectiveness (VE) against infection and hospitalization with omicron subvariants. The study includes 30,809 SARS-CoV-2 positive and 92,427 SARS-CoV-2 negative individuals aged ≥18 years tested during 1/1/2022-6/30/2022. While 3-dose VE against BA.1 infection is high and wanes slowly, VE against BA.2, BA.2.12.1, BA.4, and BA.5 infection is initially moderate to high (61.0%-90.6% 14-30 days post third dose) and wanes rapidly. The 4-dose VE against infection with BA.2, BA.2.12.1, and BA.4 ranges between 64.3%-75.7%, and is low (30.8%) against BA.5 14-30 days post fourth dose, disappearing beyond 90 days for all subvariants. The 3-dose VE against hospitalization for BA.1, BA.2, and BA.4/BA.5 is 97.5%, 82.0%, and 72.4%, respectively; 4-dose VE against hospitalization for BA.4/BA.5 is 88.5%. Evaluation of the updated bivalent booster is warranted.
Metal single-site catalyst design for electrocatalytic production of hydrogen peroxide at industrial-relevant currents
Authors: Cao Peike , Quan Xie , Nie Xiaowa , Zhao Kun , Liu Yanming , Chen Shuo , Yu Hongtao , Chen Jingguang G.
Published: January 2023

Direct hydrogen peroxide (H2O2) electrosynthesis via the two-electron oxygen reduction reaction is a sustainable alternative to the traditional energy-intensive anthraquinone technology. However, high-performance and scalable electrocatalysts with industrial-relevant production rates remain to be challenging, partially due to insufficient atomic level understanding in catalyst design. Here we utilize theoretical approaches to identify transition-metal single-site catalysts for two-electron oxygen reduction using the *OOH binding energy as a descriptor. The theoretical predictions are then used as guidance to synthesize the desired cobalt single-site catalyst with a O-modified Co-(pyrrolic N)4configuration that can achieve industrial-relevant current densities up to 300 mA cm−2with 96–100% Faradaic efficiencies for H2O2production at a record rate of 11,527 mmol h−1 gcat−1. Here, we show the feasibility and versatility of metal single-site catalyst design using various commercial carbon and cobalt phthalocyanine as starting materials and the high applicability for H2O2electrosynthesis in acidic, neutral and alkaline electrolytes.
Absence of a pressure gap and atomistic mechanism of the oxidation of pure Co nanoparticles
Authors: Vijayakumar Jaianth , Savchenko Tatiana M. , Bracher David M. , Lumbeeck Gunnar , Béché Armand , Verbeeck Jo , Vajda Štefan , Nolting Frithjof , Vaz C.A.F. , Kleibert Armin
Published: January 2023

Understanding chemical reactivity and magnetism of 3d transition metal nanoparticles is of fundamental interest for applications in fields ranging from spintronics to catalysis. Here, we present an atomistic picture of the early stage of the oxidation mechanism and its impact on the magnetism of Co nanoparticles. Our experiments reveal a two-step process characterized by (i) the initial formation of small CoO crystallites across the nanoparticle surface, until their coalescence leads to structural completion of the oxide shell passivating the metallic core; (ii) progressive conversion of the CoO shell to Co3O4 and void formation due to the nanoscale Kirkendall effect. The Co nanoparticles remain highly reactive toward oxygen during phase (i), demonstrating the absence of a pressure gap whereby a low reactivity at low pressures is postulated. Our results provide an important benchmark for the development of theoretical models for the chemical reactivity in catalysis and magnetism during metal oxidation at the nanoscale.
Self-vectoring electromagnetic soft robots with high operational dimensionality
Authors: Li Wenbo , Chen Huyue , Yi Zhiran , Fang Fuyi , Guo Xinyu , Wu Zhiyuan , Gao Qiuhua , Shao Lei , Xu Jian , Meng Guang , Zhang Wenming
Published: January 2023

Soft robots capable of flexible deformations and agile locomotion similar to biological systems are highly desirable for promising applications, including safe human-robot interactions and biomedical engineering. Their achievable degree of freedom and motional deftness are limited by the actuation modes and controllable dimensions of constituent soft actuators. Here, we report self-vectoring electromagnetic soft robots (SESRs) to offer new operational dimensionality via actively and instantly adjusting and synthesizing the interior electromagnetic vectors (EVs) in every flux actuator sub-domain of the robots. As a result, we can achieve high-dimensional operation with fewer actuators and control signals than other actuation methods. We also demonstrate complex and rapid 3D shape morphing, bioinspired multimodal locomotion, as well as fast switches among different locomotion modes all in passive magnetic fields. The intrinsic fast (re)programmability of SESRs, along with the active and selective actuation through self-vectoring control, significantly increases the operational dimensionality and possibilities for soft robots.
Recent waning snowpack in the Alps is unprecedented in the last six centuries
Authors: Carrer Marco , Dibona Raffaella , Prendin Angela Luisa , Brunetti Michele
Published: January 2023

Snow cover in high-latitude and high-altitude regions has strong effects on the Earth’s climate, environmental processes and socio-economic activities. Over the last 50 years, the Alps experienced a 5.6% reduction per decade in snow cover duration, which already affects a region where economy and culture revolve, to a large extent, around winter. Here we present evidence from 572 ring-width series extracted from a prostrate shrub (Juniperus communis L.) growing at high elevation in the Val Ventina, Italy. These ring-width records show that the duration of current snowpack cover is 36 days shorter than the long-term mean, a decline that is unprecedented over the last six centuries. These findings highlight the urgent need to develop adaptation strategies for some of the most sensitive environmental and socio-economic sectors in this region.
Macroscopic quorum sensing sustains differentiating embryonic stem cells
Authors: Daneshpour Hirad , van den Bersselaar Pim , Chao Chun-Hao , Fazzio Thomas G. , Youk Hyun
Published: January 2023

Cells can secrete molecules that help each other’s replication. In cell cultures, chemical signals might diffuse only within a cell colony or between colonies. A chemical signal’s interaction length—how far apart interacting cells are—is often assumed to be some value without rigorous justifications because molecules’ invisible paths and complex multicellular geometries pose challenges. Here we present an approach, combining mathematical models and experiments, for determining a chemical signal’s interaction length. With murine embryonic stem (ES) cells as a testbed, we found that differentiating ES cells secrete FGF4, among others, to communicate over many millimeters in cell culture dishes and, thereby, form a spatially extended, macroscopic entity that grows only if its centimeter-scale population density is above a threshold value. With this ‘macroscopic quorum sensing’, an isolated macroscopic, but not isolated microscopic, colony can survive differentiation. Our integrated approach can determine chemical signals’ interaction lengths in generic multicellular communities.
The Dresden Surgical Anatomy Dataset for Abdominal Organ Segmentation in Surgical Data Science
Authors: Carstens Matthias , Rinner Franziska M. , Bodenstedt Sebastian , Jenke Alexander C. , Weitz Jürgen , Distler Marius , Speidel Stefanie , Kolbinger Fiona R.
Published: January 2023

Laparoscopy is an imaging technique that enables minimally-invasive procedures in various medical disciplines including abdominal surgery, gynaecology and urology. To date, publicly available laparoscopic image datasets are mostly limited to general classifications of data, semantic segmentations of surgical instruments and low-volume weak annotations of specific abdominal organs. The Dresden Surgical Anatomy Dataset provides semantic segmentations of eight abdominal organs (colon, liver, pancreas, small intestine, spleen, stomach, ureter, vesicular glands), the abdominal wall and two vessel structures (inferior mesenteric artery, intestinal veins) in laparoscopic view. In total, this dataset comprises 13195 laparoscopic images. For each anatomical structure, we provide over a thousand images with pixel-wise segmentations. Annotations comprise semantic segmentations of single organs and one multi-organ-segmentation dataset including segments for all eleven anatomical structures. Moreover, we provide weak annotations of organ presence for every single image. This dataset markedly expands the horizon for surgical data science applications of computer vision in laparoscopic surgery and could thereby contribute to a reduction of risks and faster translation of Artificial Intelligence into surgical practice.
A Non-Laboratory Gait Dataset of Full Body Kinematics and Egocentric Vision
Authors: Sharma Abhishek , Rai Vijeth , Calvert Melissa , Dai Zhongyi , Guo Zhenghao , Boe David , Rombokas Eric
Published: January 2023

In this manuscript, we describe a unique dataset of human locomotion captured in a variety of out-of-the-laboratory environments captured using Inertial Measurement Unit (IMU) based wearable motion capture. The data contain full-body kinematics for walking, with and without stops, stair ambulation, obstacle course navigation, dynamic movements intended to test agility, and negotiating common obstacles in public spaces such as chairs. The dataset contains 24.2 total hours of movement data from a college student population with an approximately equal split of males to females. In addition, for one of the activities, we captured the egocentric field of view and gaze of the subjects using an eye tracker. Finally, we provide some examples of applications using the dataset and discuss how it might open possibilities for new studies in human gait analysis.
Genetic complementation fosters evolvability in complex fitness landscapes
Authors: Segredo-Otero Ernesto , Sanjuán Rafael
Published: January 2023

The ability of natural selection to optimize traits depends on the topology of the genotype-fitness map (fitness landscape). Epistatic interactions produce rugged fitness landscapes, where adaptation is constrained by the presence of low-fitness intermediates. Here, we used simulations to explore how evolvability in rugged fitness landscapes is influenced by genetic complementation, a process whereby different sequence variants mutually compensate for their deleterious mutations. We designed our model inspired by viral populations, in which genetic variants are known to interact frequently through coinfection. Our simulations indicate that genetic complementation enables a more efficient exploration of rugged fitness landscapes. Although this benefit may be undermined by genetic parasites, its overall effect on evolvability remains positive in populations that exhibit strong relatedness between interacting sequences. Similar processes could operate in contexts other than viral coinfection, such as in the evolution of ploidy.
Decoding of human identity by computer vision and neuronal vision
Authors: Zhang Yipeng , Aghajan Zahra M. , Ison Matias , Lu Qiujing , Tang Hanlin , Kalender Guldamla , Monsoor Tonmoy , Zheng Jie , Kreiman Gabriel , Roychowdhury Vwani , Fried Itzhak
Published: January 2023

Extracting meaning from a dynamic and variable flow of incoming information is a major goal of both natural and artificial intelligence. Computer vision (CV) guided by deep learning (DL) has made significant strides in recognizing a specific identity despite highly variable attributes. This is the same challenge faced by the nervous system and partially addressed by the concept cells—neurons exhibiting selective firing in response to specific persons/places, described in the human medial temporal lobe (MTL) ⁠. Yet, access to neurons representing a particular concept is limited due to these neurons’ sparse coding. It is conceivable, however, that the information required for such decoding is present in relatively small neuronal populations. To evaluate how well neuronal populations encode identity information in natural settings, we recorded neuronal activity from multiple brain regions of nine neurosurgical epilepsy patients implanted with depth electrodes, while the subjects watched an episode of the TV series “24”. First, we devised a minimally supervised CV algorithm (with comparable performance against manually-labeled data) to detect the most prevalent characters (above 1% overall appearance) in each frame. Next, we implemented DL models that used the time-varying population neural data as inputs and decoded the visual presence of the four main characters throughout the episode. This methodology allowed us to compare “computer vision” with “neuronal vision”—footprints associated with each character present in the activity of a subset of neurons—and identify the brain regions that contributed to this decoding process. We then tested the DL models during a recognition memory task following movie viewing where subjects were asked to recognize clip segments from the presented episode. DL model activations were not only modulated by the presence of the corresponding characters but also by participants’ subjective memory of whether they had seen the clip segment, and by the associative strengths of the characters in the narrative plot. The described approach can offer novel ways to probe the representation of concepts in time-evolving dynamic behavioral tasks. Further, the results suggest that the information required to robustly decode concepts is present in the population activity of only tens of neurons even in brain regions beyond MTL.
Comparative metabolic profiling of olive leaf extracts from twelve different cultivars collected in both fruiting and flowering seasons
Authors: Kabbash Eman M. , Abdel-Shakour Zeinab T. , El-Ahmady Sherweit H. , Wink Michael , Ayoub Iriny M.
Published: January 2023

Olea europaea is an economically significant crop native to Mediterranean countries. Its leaves exhibit several biological properties associated to their chemical composition. The aqueous ethanolic extracts of olive leaves from twelve different cultivars were analyzed by high performance liquid chromatography coupled to photodiode array and electrospray ionization mass spectrometry (HPLC/PDA/ESI–MS/MS). A total of 49 phytochemicals were identified in both positive and negative ionization modes. The identified compounds belonged to four classes of secondary metabolites including secoiridoids, flavonoids, pentacyclic triterpenoids and various phenolic compounds. Seasonal variation in chemical composition among the studied cultivars was apparent in autumn and spring. Secologanoside, oleuropein, hydroxy-oleuropein, demethyl oleuropein, gallocatechin, luteolin-O-hexoside, diosmetin, oleanolic acid and maslinic acid were detected in all cultivars in both seasons. Oleuropein-O-deoxyhexoside was tentatively identified for the first time in olive leaf extracts; detected only in the Spanish cultivar Picual (PIC) collected in spring. Also, dihydroxy-oxooleanenoic acid and hydroxy-oxooleanenoic acid, two bioactive pentacyclic triterpenes, were identified. Principle component analysis (PCA) showed good discrimination among the studied cultivars in terms of their botanical origin. This study is considered the first study for non-targeted metabolic profiling of different olive leaf cultivars cultivated in Egypt.
Potentially toxic elements in the brains of people with multiple sclerosis
Authors: Pamphlett Roger , Buckland Michael E. , Bishop David P.
Published: January 2023

Potentially toxic elements such as lead and aluminium have been proposed to play a role in the pathogenesis of multiple sclerosis (MS), since their neurotoxic mechanisms mimic many of the pathogenetic processes in MS. We therefore examined the distribution of several potentially toxic elements in the autopsied brains of people with and without MS, using two methods of elemental bio-imaging. Toxicants detected in the locus ceruleus were used as indicators of past exposures. Autometallography of paraffin sections from multiple brain regions of 21 MS patients and 109 controls detected inorganic mercury, silver, or bismuth in many locus ceruleus neurons of both groups, and in widespread blood vessels, oligodendrocytes, astrocytes, and neurons of four MS patients and one control. Laser ablation-inductively coupled plasma-mass spectrometry imaging of pons paraffin sections from all MS patients and 12 controls showed that combinations of iron, silver, lead, aluminium, mercury, nickel, and bismuth were present more often in the locus ceruleus of MS patients and were located predominantly in white matter tracts. Based on these results, we propose that metal toxicants in locus ceruleus neurons weaken the blood–brain barrier, enabling multiple interacting toxicants to pass through blood vessels and enter astrocytes and oligodendroglia, leading to demyelination.
Nutritional epigenomic and DNA-damage modulation effect of natural stilbenoids
Authors: Volpes Sara , Cruciata Ilenia , Ceraulo Federica , Schimmenti Chiara , Naselli Flores , Pinna Cecilia , Mauro Maurizio , Picone Pasquale , Dallavalle Sabrina , Nuzzo Domenico , Pinto Andrea , Caradonna Fabio
Published: January 2023

The aim of the present work is the evaluation of biological effects of natural stilbenoids found in Vitis vinifera, with a focus on their activity as epigenetic modulators. In the present study, resveratrol, pterostilbene and for the first time their dimers (±)-trans-δ-viniferin, (±)-trans-pterostilbene dehydrodimer were evaluated in Caco-2 and HepG-2 cell lines as potential epigenetic modulators. Stilbenoids were added in a Caco-2 cell culture as a model of the intestinal epithelial barrier and in the HepG-2 as a model of hepatic environment, to verify their dose-dependent toxicity, ability to interact with DNA, and epigenomic action. Resveratrol, pterostilbene, and (±)-trans-pterostilbene dehydrodimer were found to have no toxic effects at tested concentration and were effective in reversing arsenic damage in Caco-2 cell lines. (±)-trans-δ-viniferin showed epigenomic activity, but further studies are needed to clarify its mode of action.
Prediction of type 2 diabetes mellitus using hematological factors based on machine learning approaches: a cohort study analysis
Authors: Mansoori Amin , Sahranavard Toktam , Hosseini Zeinab Sadat , Soflaei Sara Saffar , Emrani Negar , Nazar Eisa , Gharizadeh Melika , Khorasanchi Zahra , Effati Sohrab , Ghamsary Mark , Ferns Gordon , Esmaily Habibollah , Mobarhan Majid Ghayour
Published: January 2023

Type 2 Diabetes Mellitus (T2DM) is a significant public health problem globally. The diagnosis and management of diabetes are critical to reduce the diabetes complications including cardiovascular disease and cancer. This study was designed to assess the potential association between T2DM and routinely measured hematological parameters. This study was a subsample of 9000 adults aged 35–65 years recruited as part of Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study. Machine learning techniques including logistic regression (LR), decision tree (DT) and bootstrap forest (BF) algorithms were applied to analyze data. All data analyses were performed using SPSS version 22 and SAS JMP Pro version 13 at a significant level of 0.05. Based on the performance indices, the BF model gave high accuracy, precision, specificity, and AUC. Previous studies suggested the positive relationship of triglyceride-glucose (TyG) index with T2DM, so we considered the association of TyG index with hematological factors. We found this association was aligned with their results regarding T2DM, except MCHC. The most effective factors in the BF model were age and WBC (white blood cell). The BF model represented a better performance to predict T2DM. Our model provides valuable information to predict T2DM like age and WBC.
Converging orifice used to control the discharge rate of spherical particles from a flat floor silo
Authors: Wiącek Joanna , Horabik Józef , Molenda Marek , Parafiniuk Piotr , Bańda Maciej , Stasiak Mateusz
Published: January 2023

The effect of the converging orifice geometry in a model silo on the discharge rate of monosized spherical particles was studied experimentally and numerically. The cylindrical container was equipped with interchangeable inserts with converging discharge orifices of various upper diameters in the upper base and a constant lower diameter in the lower base. Plastic PLA beads and agricultural granular materials: wheat, rapeseeds, and linseeds were tested. A series of discrete element method simulations corresponding to the performed experiments was conducted with a largely extended set of experimental discharge conditions. In the case of the constant thickness of the insert, the discharge rate initially increased with an increase in the half cone angle of the converging orifice and then the tendency reversed. In the majority of cases, the discharge rate through the converging orifice was higher than through the hopper with the same orifice diameter.
Trogocytosis of neurons and glial cells by microglia in a healthy adult macaque retina
Authors: Goyal Megan , Bordt Andrea S. , Neitz Jay , Marshak David W.
Published: January 2023

Microglial cells are the primary resident immune cells in the retina. In healthy adults, they are ramified; that is, they have extensive processes that move continually. In adult retinas, microglia maintain the normal structure and function of neurons and other glial cells, but the mechanism underlying this process is not well-understood. In the mouse hippocampus, microglia engulf small pieces of axons and presynaptic terminals via a process called trogocytosis. Here we report that microglia in the adult macaque retina also engulf pieces of neurons and glial cells, but not at sites of synapses. We analyzed microglia in a volume of serial, ultrathin sections of central macaque retina in which many neurons that ramify in the inner plexiform layer (IPL) had been reconstructed previously. We surveyed the IPL and identified the somas of microglia by their small size and scant cytoplasm. We then reconstructed the microglia and studied their interactions with other cells. We found that ramified microglia frequently ingested small pieces of each major type of inner retinal neuron and Müller glial cells via trogocytosis. There were a few instances where the interactions took place near synapses, but the synapses, themselves, were never engulfed. If trogocytosis by retinal microglia plays a role in synaptic remodeling, it was not apparent from the ultrastructure. Instead, we propose that trogocytosis enables these microglia to present antigens derived from normal inner retinal cells and, when activated, they would promote antigen-specific tolerance.