bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes
Authors: Zorko Nicholas A. , Makovec Allison , Elliott Andrew , Kellen Samuel , Lozada John R. , Arafa Ali T. , Felices Martin , Shackelford Madison , Barata Pedro , Zakharia Yousef , Narayan Vivek , Stein Mark N. , Zarrabi Kevin K. , Patniak Akash , Bilen Mehmet A. , Radovich Milan , Sledge George , El-Deiry Wafik S. , Heath Elisabeth I. , Hoon Dave S. B. , Nabhan Chadi , Miller Jeffrey S. , Hwang Justin H. , Antonarakis Emmanuel S.
Published: February 2024

Background

Natural killer (NK) cells are non-antigen specific innate immune cells that can be redirected to targets of interest using multiple strategies, although none are currently FDA-approved. We sought to evaluate NK cell infiltration into tumors to develop an improved understanding of which histologies may be most amenable to NK cell-based therapies currently in the developmental pipeline.

Methods

DNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from tumors from 45 cancer types (N = 90,916 for all cancers and N = 3365 for prostate cancer) submitted to Caris Life Sciences. NK cell fractions and immune deconvolution were inferred from RNA-seq data using quanTIseq. Real-world overall survival (OS) and treatment status was determined and Kaplan–Meier estimates were calculated. Statistical significance was determined using X2 and Mann–Whitney U tests, with corrections for multiple comparisons where appropriate.

Results

In both a pan-tumor and prostate cancer (PCa) -specific setting, we demonstrated that NK cells represent a substantial proportion of the total cellular infiltrate (median range 2–9% for all tumors). Higher NK cell infiltration was associated with improved OS in 28 of 45 cancer types, including (PCa). NK cell infiltration was negatively correlated with common driver mutations and androgen receptor variants (AR-V7) in primary prostate biopsies, while positively correlated with negative immune regulators. Higher levels of NK cell infiltration were associated with patterns consistent with a compensatory anti-inflammatory response.

Conclusions

Using the largest available dataset to date, we demonstrated that NK cells infiltrate a broad range of tumors, including both primary and metastatic PCa. NK cell infiltration is associated with improved PCa patient outcomes. This study demonstrates that NK cells are capable of trafficking to both primary and metastatic PCa and are a viable option for immunotherapy approaches moving forward. Future development of strategies to enhance tumor-infiltrating NK cell-mediated cytolytic activity and activation while limiting inhibitory pathways will be key.
Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity
Authors: Zhou Jun , Liu Jiaqi , Wang Bingjing , Li Nan , Liu Juan , Han Yanmei , Cao Xuetao
Published: February 2024

Memory CD8+ T cell generation is crucial for pathogen elimination and effective vaccination against infection. The cellular and molecular circuitry that underlies the generation of memory CD8+ T cells remains elusive. Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense. Here we report that eosinophils are required for the generation of memory CD8+ T cells by inhibiting CD8+ T cell apoptosis. Eosinophil-deficient mice display significantly impaired memory CD8+ T cell response and weakened resistance against Listeria monocytogenes (L.m.) infection. Mechanistically, eosinophils secrete interleukin-4 (IL-4) to inhibit JNK/Caspase-3 dependent apoptosis of CD8+ T cells upon L.m. infection in vitro. Furthermore, active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+ T cell apoptosis during early stage of L.m. infection in vivo. Adoptive transfer of wild-type (WT) eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+ T cell memory responses. Together, our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+ T cell memory and enhances immune defense against L.m. infection. Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.
Diminished NAD+ levels and activation of retrotransposons promote postovulatory aged oocyte (POAO) death
Authors: Singh Ajay K. , Mohanty Aradhana , Kumar S. Lava , Kumari Anjali , Beniwal Rohit , Kumar Etikuppam Ajith , Birajdar Pravin , Mohd Athar , Prasada Rao H. B. D.
Published: February 2024

Death is the fate of postovulatory aged or unfertilized oocytes (POAO) in many animals. However, precise molecular mechanisms are yet to be discovered. Here, we demonstrate that increased amounts of reactive oxygen species (ROS), calcium ion (Ca+2) channels, and retrotransposon activity induce apoptosis, which in turn causes POAO death. Notably, suppression of ROS, Ca+2 channels, and retrotransposons delayed POAO death. Further, we found that the histone H4K12 and K16 acetylation increased via downregulation of NAD+ and NAD+ -dependent histone deacetylase SIRT3. Furthermore, adding NMN, sodium pyruvate, or CD38 inhibition delayed the death of postovulatory aged oocytes. Finally, we demonstrate the conservation of retrotransposon-induced DNA damage-dependent POAO death in higher-order vertebrates. Our findings suggest that POAO mortality is caused by cyclic cascade metabolic interactions in which low NAD+ levels increase histone acetylation by inhibiting histone deacetylases, resulting in an increase in retrotransposons, ROS, and Ca+2 channel activity and thus contributing to DNA damage-induced apoptosis.
Structure-function analysis of the cyclic β-1,2-glucan synthase from Agrobacterium tumefaciens
Authors: Sedzicki Jaroslaw , Ni Dongchun , Lehmann Frank , Stahlberg Henning , Dehio Christoph
Published: February 2024

The synthesis of complex sugars is a key aspect of microbial biology. Cyclic β-1,2-glucan (CβG) is a circular polysaccharide critical for host interactions of many bacteria, including major pathogens of humans (Brucella) and plants (Agrobacterium). CβG is produced by the cyclic glucan synthase (Cgs), a multi-domain membrane protein. So far, its structure as well as the mechanism underlining the synthesis have not been clarified. Here we use cryo-electron microscopy (cryo-EM) and functional approaches to study Cgs from A. tumefaciens. We determine the structure of this complex protein machinery and clarify key aspects of CβG synthesis, revealing a distinct mechanism that uses a tyrosine-linked oligosaccharide intermediate in cycles of polymerization and processing of the glucan chain. Our research opens possibilities for combating pathogens that rely on polysaccharide virulence factors and may lead to synthetic biology approaches for producing complex cyclic sugars.
Disentangling the multiorbital contributions of excitons by photoemission exciton tomography
Authors: Bennecke Wiebke , Windischbacher Andreas , Schmitt David , Bange Jan Philipp , Hemm Ralf , Kern Christian S. , D’Avino Gabriele , Blase Xavier , Steil Daniel , Steil Sabine , Aeschlimann Martin , Stadtmüller Benjamin , Reutzel Marcel , Puschnig Peter , Jansen G. S. Matthijs , Mathias Stefan
Published: February 2024

Excitons are realizations of a correlated many-particle wave function, specifically consisting of electrons and holes in an entangled state. Excitons occur widely in semiconductors and are dominant excitations in semiconducting organic and low-dimensional quantum materials. To efficiently harness the strong optical response and high tuneability of excitons in optoelectronics and in energy-transformation processes, access to the full wavefunction of the entangled state is critical, but has so far not been feasible. Here, we show how time-resolved photoemission momentum microscopy can be used to gain access to the entangled wavefunction and to unravel the exciton’s multiorbital electron and hole contributions. For the prototypical organic semiconductor buckminsterfullerene (C60), we exemplify the capabilities of exciton tomography and achieve unprecedented access to key properties of the entangled exciton state including localization, charge-transfer character, and ultrafast exciton formation and relaxation dynamics.
Molecular and clinical analyses of PHF6 mutant myeloid neoplasia provide their pathogenesis and therapeutic targeting
Authors: Kubota Yasuo , Gu Xiaorong , Terkawi Laila , Bodo Juraj , Przychodzen Bartlomiej P. , Awada Hussein , Williams Nakisha , Gurnari Carmelo , Kawashima Naomi , Aly Mai , Durmaz Arda , Mori Minako , Ponvilawan Ben , Kewan Tariq , Bahaj Waled , Meggendorfer Manja , Jha Babal K. , Visconte Valeria , Rogers Heesun J. , Haferlach Torsten , Maciejewski Jaroslaw P.
Published: February 2024

PHF6 mutations (PHF6MT) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Here we show three main findings in our comprehensive genomic and proteomic study. Firstly, we show a different pattern of genes correlating with PHF6MT in male and female cases. When analyzing male and female cases separately, in only male cases, RUNX1 and U2AF1 are co-mutated with PHF6. In contrast, female cases reveal co-occurrence of ASXL1 mutations and X-chromosome deletions with PHF6MT. Next, proteomics analysis reveals a direct interaction between PHF6 and RUNX1. Both proteins co-localize in active enhancer regions that define the context of lineage differentiation. Finally, we demonstrate a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival are additive as PHF6MT cases with RUNX1 mutations have worse outcomes when compared to cases carrying single mutation or wild-type.
An atlas of epithelial cell states and plasticity in lung adenocarcinoma
Authors: Han Guangchun , Sinjab Ansam , Rahal Zahraa , Lynch Anne M. , Treekitkarnmongkol Warapen , Liu Yuejiang , Serrano Alejandra G. , Feng Jiping , Liang Ke , Khan Khaja , Lu Wei , Hernandez Sharia D. , Liu Yunhe , Cao Xuanye , Dai Enyu , Pei Guangsheng , Hu Jian , Abaya Camille , Gomez-Bolanos Lorena I. , Peng Fuduan , Chen Minyue , Parra Edwin R. , Cascone Tina , Sepesi Boris , Moghaddam Seyed Javad , Scheet Paul , Negrao Marcelo V. , Heymach John V. , Li Mingyao , Dubinett Steven M. , Stevenson Christopher S. , Spira Avrum E. , Fujimoto Junya , Solis Luisa M. , Wistuba Ignacio I. , Chen Jichao , Wang Linghua , Kadara Humam
Published: February 2024

Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention.
Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells
Authors: Guan Xiangnan , Hu Ruozhen , Choi Yoonha , Srivats Shyam , Nabet Barzin Y. , Silva John , McGinnis Lisa , Hendricks Robert , Nutsch Katherine , Banta Karl L. , Duong Ellen , Dunkle Alexis , Chang Patrick S. , Han Chia-Jung , Mittman Stephanie , Molden Nandini , Daggumati Pallavi , Connolly Wendy , Johnson Melissa , Abreu Delvys Rodriguez , Cho Byoung Chul , Italiano Antoine , Gil-Bazo Ignacio , Felip Enriqueta , Mellman Ira , Mariathasan Sanjeev , Shames David S. , Meng Raymond , Chiang Eugene Y. , Johnston Robert J. , Patil Namrata S.
Published: February 2024

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.
Multisensory gamma stimulation promotes glymphatic clearance of amyloid
Authors: Murdock Mitchell H. , Yang Cheng-Yi , Sun Na , Pao Ping-Chieh , Blanco-Duque Cristina , Kahn Martin C. , Kim TaeHyun , Lavoie Nicolas S. , Victor Matheus B. , Islam Md Rezaul , Galiana Fabiola , Leary Noelle , Wang Sidney , Bubnys Adele , Ma Emily , Akay Leyla A. , Sneve Madison , Qian Yong , Lai Cuixin , McCarthy Michelle M. , Kopell Nancy , Kellis Manolis , Piatkevich Kiryl D. , Boyden Edward S. , Tsai Li-Huei
Published: February 2024

The glymphatic movement of fluid through the brain removes metabolic waste1–4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease5–8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.
Quantitative risk factor analysis of prior disease condition and socioeconomic status with the multiple myeloma development: nationwide cohort study
Authors: Choi Suein , Kim Eunjin , Jung Jinhee , Park Sung-Soo , Min Chang-Ki , Han Seunghoon
Published: February 2024

Early diagnosis and following management are important determinants of the prognosis of multiple myeloma (MM). However, screening for MM is not routinely performed because it is rare disease. In this study, we evaluated the association of prior disease condition and socioeconomic status (SES) with MM diagnosis and developed a simple predictive model that can identify patients at high risk of developing MM who may need screening using nationwide database from South Korea. According to multivariate logistic regression analysis, eight prior disease conditions and SES before diagnosis were shown to be predictors of MM development and selected for score development. Total prediction scores were categorized into four groups: patients without any risk (≤ 0) intermediate-1 (0.5–9), intermediate-2 (9–14), and high risk (> 14). The odds ratios for developing MM in the intermediate-1, intermediate-2, and high-risk groups were 1.29, 3.07, and 4.62, respectively. The association of prior disease conditions and SES with MM diagnosis were demonstrated and the simple scoring system to predict the MM risk was developed. This scoring system is also provided by web-based application and could be a useful tool to support clinicians in identifying potential candidates for MM screening.
Conjugating uncoupler compounds with hydrophobic hydrocarbon chains to achieve adipose tissue selective drug accumulation
Authors: Ng Mei Ying , Song Zhi Jian , Venkatesan Gopalakrishnan , Rodriguez-Cuenca Sergio , West James A. , Yang Shili , Tan Choon Hong , Ho Paul Chi-Lui , Griffin Julian L. , Vidal-Puig Antonio , Bassetto Marcella , Hagen Thilo
Published: February 2024

One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes. Hence, we explored the feasibility of conjugating uncoupler compounds with a lipophilic C8-hydrocarbon chain via an ether bond. We found that substituting the trifluoromethoxy group in the uncoupler FCCP with a C8-hydrocarbon chain resulted in potent uncoupling activity. Nonetheless, the compound did not elicit therapeutic effects in mice, likely as a consequence of metabolic instability resulting from rapid ether bond cleavage. A lipophilic analog of the uncoupler compound 2,6-dinitrophenol, in which a C8-hydrocarbon chain was conjugated via an ether bond in the para-position (2,6-dinitro-4-(octyloxy)phenol), exhibited increased uncoupling activity compared to the parent compound. However, in vivo pharmacokinetics studies suggested that 2,6-dinitro-4-(octyloxy)phenol was also metabolically unstable. In conclusion, conjugation of a hydrophobic hydrocarbon chain to uncoupler compounds resulted in sustained or improved uncoupling activity. However, an ether bond linkage led to metabolic instability, indicating the need to conjugate lipophilic groups via other chemical bonds.
High rate of species misidentification reduces the taxonomic certainty of European biodiversity databases of ivies (Hedera L.)
Authors: Coca-de-la-Iglesia Marina , Gallego-Narbón Angélica , Alonso Alejandro , Valcárcel Virginia
Published: February 2024

The digitization of natural history specimens and the popularization of citizen science are creating an unprecedented availability of large amounts of biodiversity data. These biodiversity inventories can be severely affected by species misidentification, a source of taxonomic uncertainty that is rarely acknowledged in biodiversity data management. For these reasons, taxonomists debate the use of online repositories to address biological questions at the species level. Hedera L. (ivies) provides an excellent case study as it is well represented in both herbaria and online repositories with thousands of records likely to be affected by high taxonomic uncertainty. We analyze the sources and extent of taxonomic errors in the identification of the European ivy species by reviewing herbarium specimens and find a high misidentification rate (18% on average), which varies between species (maximized in H. hibernica: 55%; H. azorica: 48%; H. iberica: 36%) and regions (maximized in the UK: 38% and Spain: 27%). We find a systematic misidentification of all European ivies with H. helix behind the high misidentification rates in herbaria and warn of even higher rates in online records. We compile a spatial database to overcome the large discrepancies we observed in species distributions between online and morphologically reviewed records.
Interaction between body mass index and family history of cancer on the risk of female breast cancer
Authors: Cao Jiamin , Li Jun , Zhang Zuofeng , Qin Guoyou , Pang Yi , Wu Mengyin , Gu Kai , Xu Huilin
Published: February 2024

Both body mass index (BMI) and family history of cancer are established risk factors for female breast cancer. However, few studies explored the potential interaction between both factors. We assessed the association of BMI and its interaction with family cancer history on the risk of female breast cancer in Shanghai, China. Based on a population-based prospective cohort study started from 2008 to 2012 with 15,055 Chinese female participants in Minhang district, Shanghai. Cox regression models were used to estimate the association of BMI and its interaction with a family history of cancer on breast cancer risk. The additive interaction was evaluated by the relative excess risk due to interaction (RERI) and the attributable proportion due to interaction (AP), and the multiplicative interaction was assessed by the product term (BMI* family history of cancer) in the Cox regression model. Compared with BMI of < 24 kg/m2 and no family history of cancer, women with BMI of ≥ 24 kg/m2 and a family history of cancer had a higher risk for breast cancer with HR 2.06 (95% CI 1.39, 3.06). There was an additive interaction between BMI and family history of cancer on breast cancer incidence, with the RERI being 0.29 (95% CI 0.08, 0.51) and the AP being 0.37 (95% CI 0.08, 0.66). The coexistence of obesity and cancer family history may exacerbate breast cancer incidence risk, highlighting the importance of weight management in women with a family history of cancer.
Cytotoxic and antiviral activities of Jatropha variegata and Jatropha spinosa in relation to their metabolite profile
Authors: Shari Khawlah , Mohamed Osama G. , Meselhy Khaled M. , Tripathi Ashootosh , Khaleel Amal E. , Abdel-Sattar Essam , Gedaily Rania A. El
Published: February 2024

Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata (F-6) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC50 = 1.4 and 1 μg/mL), HepG2 (IC50 = 0.64 and 0.24 μg/mL), and A549 (IC50 = 0.7 and 0.5 μg/mL), respectively, whereas the IC50 values of the standard doxorubicin were (3.83, 4.73, and 4.57 μg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC50 of 101.23, 68.83, 4.88, 3.24 μg/mL and against H1N1 with IC50 of 51.29, 27.92, 4.24, and 3.06 μg/mL respectively, whereas the IC50 value of the standard acyclovir against HVS-2 was 83.19 μg/mL and IC50 value of the standard ribavirin against H1N1 was 52.40 μg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.
Production of iron enriched Saccharomyces boulardii: impact of process variables
Authors: Tafazzoli Kiyana , Ghavami Mehrdad , Khosravi-Darani Kianoush
Published: February 2024

About half of the 1.62 billion cases of anemia are because of poor diet and iron deficiency. Currently, the use of iron-enriched yeasts can be used as the most effective and possible way to prevent and treat anemia due to the ability of biotransformation of mineral compounds into the organic form. In this research, for the first time, Saccharomyces (S.) boulardii was used for iron enrichment with the aim that the probiotic properties of yeast provide a potential iron supplement besides improving the bioavailability of iron. Also, due to its higher resistance than other Saccharomyces strains against stresses, it can protect iron against processing temperatures and stomach acidic-enzymatic conditions. So, the effect of three important variables, including concentration of iron, molasses and KH2PO4 on the growth and biotransformation of yeast was investigated by the Box-Behnken design (BBD). The best conditions occurred in 3 g/l KH2PO4, 20 g/l molasses and 12 mg/l FeSO4 with the highest biotransformation 27 mg Fe/g dry cell weight (DCW) and 6 g/l biomass weight. Such yeast can improve fermented products, provide potential supplement, and restore the lost iron of bread, which is a useful iron source, even for vegetarians-vegans and play an important role in manage with anemia. It is recommended that in future researches, attention should be paid to increasing the iron enrichment of yeast through permeabilizing the membrane and overcoming the structural barrier of the cell wall.
Assessing the perceived effect of non-pharmaceutical interventions on SARS-Cov-2 transmission risk: an experimental study in Europe
Authors: Veltri Giuseppe Alessandro , Steinert Janina Isabel , Sternberg Henrike , Galizzi Matteo M. , Fasolo Barbara , Kourtidis Ploutarchos , Büthe Tim , Gaskell George
Published: February 2024

We conduct a large (N = 6567) online experiment to measure the features of non-pharmaceutical interventions (NPIs) that citizens of six European countries perceive to lower the risk of transmission of SARS-Cov-2 the most. We collected data in Bulgaria (n = 1069), France (n = 1108), Poland (n = 1104), Italy (n = 1087), Spain (n = 1102) and Sweden (n = 1097). Based on the features of the most widely adopted public health guidelines to reduce SARS-Cov-2 transmission (mask wearing vs not, outdoor vs indoor contact, short vs 90 min meetings, few vs many people present, and physical distancing of 1 or 2 m), we conducted a discrete choice experiment (DCE) to estimate the public’s perceived risk of SARS-CoV-2 transmission in scenarios that presented mutually exclusive constellations of these features. Our findings indicate that participants’ perception of transmission risk was most influenced by the NPI attributes of mask-wearing and outdoor meetings and the least by NPI attributes that focus on physical distancing, meeting duration, and meeting size. Differentiating by country, gender, age, cognitive style (reflective or intuitive), and perceived freight of COVID-19 moreover allowed us to identify important differences between subgroups. Our findings highlight the importance of improving health policy communication and citizens’ health literacy about the design of NPIs and the transmission risk of SARS-Cov-2 and potentially future viruses.
Date fruit melanin is primarily based on (−)-epicatechin proanthocyanidin oligomers
Authors: Alam Muneeba Zubair , Okonkwo Clinton Emeka , Cachaneski-Lopes João P. , Graeff Carlos F. O. , Batagin-Neto Augusto , Tariq Saeed , Varghese Sabu , O’Connor Matthew J. , Albadri Abuzar E. , Webber J. Beau W. , Tarique Mohammed , Ayyash Mutamed , Kamal-Eldin Afaf
Published: February 2024

Plant-based melanin seems to be abundant, but it did not receive scientific attention despite its importance in plant biology and medicinal applications, e.g. photoprotection, radical scavenging, antimicrobial properties, etc. Date fruit melanin (DM) has complex, graphene-like, polymeric structure that needs characterization to understand its molecular properties and potential applications. This study provides the first investigation of the possible molecular composition of DM. High performance size-exclusion chromatography (HPSEC) suggested that DM contains oligomeric structures (569–3236 Da) and transmission electron microscopy (TEM) showed agglomeration of these structures in granules of low total porosity (10–1000 Å). Nuclear magnetic resonance (NMR) spectroscopy provided evidence for the presence of oligomeric proanthocyanidins and electron paramagnetic resonance (EPR) spectroscopy revealed a g-factor in the range 2.0034–2.005. Density functional theory (DFT) calculations suggested that the EPR signals can be associated with oligomeric proanthocyanidin structures having 4 and above molecular units of (−)-epicatechin. The discovery of edible melanin in date fruits and its characterization are expected to open a new area of research on its significance to nutritional and sensory characteristics of plant-based foods.
Removal of Cr(VI) from aqueous solution using ball mill modified biochar: multivariate modeling, optimization and experimental study
Authors: Tan Yunfeng , Wang Jinxia , Zhan Lingling , Yang Hongjun , Gong Yinchun
Published: February 2024

Chromium (Cr(VI)) pollution has attracted wide attention due to its high toxicity and carcinogenicity. Modified biochar has been widely used in the removal of Cr(VI) in water as an efficient and green adsorbent. However, the existing biochar prepared by chemical modification is usually complicated in process, high in cost, and has secondary pollution, which limits its application. It is urgent to explore modified biochar with simple process, low cost and environmental friendliness. Therefore, ball milling wheat straw biochar (BM-WB) was prepared by ball milling technology in this paper. The adsorption characteristics and mechanism of Cr(VI) removal by BM-WB were analyzed by functional group characterization, adsorption model and response surface method. The results showed that ball milling effectively reduced the particle size of biochar, increased the specific surface area, and more importantly, enhanced the content of oxygen-containing functional groups on the surface of biochar. After ball milling, the adsorption capacity of Cr(VI) increased by 3.5–9.1 times, and the adsorption capacity reached 52.21 mg/g. The adsorption behavior of Cr(VI) follows the pseudo-second-order kinetics and Langmuir isotherm adsorption model rate. Moreover, the Cr(VI) adsorption process of BM-WB is endothermic and spontaneous. Under the optimized conditions of pH 2, temperature 45 °C, and adsorbent dosage 0.1 g, the removal rate of Cr(VI) in the solution can reach 100%. The mechanism of Cr(VI) adsorption by BM-WB is mainly based on electrostatic attraction, redox and complexation. Therefore, ball milled biochar is a cheap, simple and efficient Cr(VI) removal material, which has a good application prospect in the field of remediation of Cr(VI) pollution in water.
Impact of florfenicol dosing regimen on the phenotypic and genotypic resistance of enteric bacteria in steers
Authors: Halleran Jennifer , Sylvester Hannah , Jacob Megan , Callahan Benjamin , Baynes Ronald , Foster Derek
Published: February 2024

The food animal sector’s use of antimicrobials is heavily critiqued for its role in allowing resistance to develop against critically important antimicrobials in human health. The WHO recommends using lower tier antimicrobials such as florfenicol for disease treatment. The primary objective of this study was to assess the differences in resistance profiles of enteric microbes following administration of florfenicol to steers using both FDA-approved dosing regimens and two different detection methods. Our hypothesis was that we would identify an increased prevalence of resistance in the steers administered the repeated, lower dose of florfenicol; additionally, we hypothesized resistance profiles would be similar between both detection methods. Twelve steers were administered either two intramuscular (20 mg/kg q 48 h; n = 6) or a single subcutaneous dose (40 mg/kg, n = 6). Fecal samples were collected for 38 days, and E. coli and Enterococcus were isolated and tested for resistance. Fecal samples were submitted for metagenomic sequencing analysis. Metagenomics revealed genes conferring resistance to aminoglycosides as the most abundant drug class. Most multidrug resistance genes contained phenicols. The genotypic and phenotypic patterns of resistance were not similar between drug classes. Observed increases in resistant isolates and relative abundance of resistance genes peaked after drug administration and returned to baseline by the end of the sampling period. The use of a “lower tier” antimicrobial, such as florfenicol, may cause an increased amount of resistance to critically important antimicrobials for a brief period, but these changes largely resolve by the end of the drug withdrawal period.
Machine learning driven web-based app platform for the discovery of monoamine oxidase B inhibitors
Authors: Kumar Sunil , Bhowmik Ratul , Oh Jong Min , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Al‑Serwi Rasha Hamed , Kim Hoon , Mathew Bijo
Published: February 2024

Monoamine oxidases (MAOs), specifically MAO-A and MAO-B, play important roles in the breakdown of monoamine neurotransmitters. Therefore, MAO inhibitors are crucial for treating various neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, we developed a novel cheminformatics pipeline by generating three diverse molecular feature-based machine learning-assisted quantitative structural activity relationship (ML-QSAR) models concerning MAO-B inhibition. PubChem fingerprints, substructure fingerprints, and one-dimensional (1D) and two-dimensional (2D) molecular descriptors were implemented to unravel the structural insights responsible for decoding the origin of MAO-B inhibition in 249 non-reductant molecules. Based on a random forest ML algorithm, the final PubChem fingerprint, substructure fingerprint, and 1D and 2D molecular descriptor prediction models demonstrated significant robustness, with correlation coefficients of 0.9863, 0.9796, and 0.9852, respectively. The significant features of each predictive model responsible for MAO-B inhibition were extracted using a comprehensive variance importance plot (VIP) and correlation matrix analysis. The final predictive models were further developed as a web application, MAO-B-pred (https://mao-b-pred.streamlit.app/), to allow users to predict the bioactivity of molecules against MAO-B. Molecular docking and dynamics studies were conducted to gain insight into the atomic-level molecular interactions between the ligand-receptor complexes. These findings were compared with the structural features obtained from the ML-QSAR models, which supported the mechanistic understanding of the binding phenomena. The presented models have the potential to serve as tools for identifying crucial molecular characteristics for the rational design of MAO-B target inhibitors, which may be used to develop effective drugs for neurodegenerative disorders.
Personalized mood prediction from patterns of behavior collected with smartphones
Authors: Balliu Brunilda , Douglas Chris , Seok Darsol , Shenhav Liat , Wu Yue , Chatzopoulou Doxa , Kaiser William , Chen Victor , Kim Jennifer , Deverasetty Sandeep , Arnaudova Inna , Gibbons Robert , Congdon Eliza , Craske Michelle G. , Freimer Nelson , Halperin Eran , Sankararaman Sriram , Flint Jonathan
Published: February 2024

Over the last ten years, there has been considerable progress in using digital behavioral phenotypes, captured passively and continuously from smartphones and wearable devices, to infer depressive mood. However, most digital phenotype studies suffer from poor replicability, often fail to detect clinically relevant events, and use measures of depression that are not validated or suitable for collecting large and longitudinal data. Here, we report high-quality longitudinal validated assessments of depressive mood from computerized adaptive testing paired with continuous digital assessments of behavior from smartphone sensors for up to 40 weeks on 183 individuals experiencing mild to severe symptoms of depression. We apply a combination of cubic spline interpolation and idiographic models to generate individualized predictions of future mood from the digital behavioral phenotypes, achieving high prediction accuracy of depression severity up to three weeks in advance (R2≥ 80%) and a 65.7% reduction in the prediction error over a baseline model which predicts future mood based on past depression severity alone. Finally, our study verified the feasibility of obtaining high-quality longitudinal assessments of mood from a clinical population and predicting symptom severity weeks in advance using passively collected digital behavioral data. Our results indicate the possibility of expanding the repertoire of patient-specific behavioral measures to enable future psychiatric research.
Summer heatwaves on the Baltic Sea seabed contribute to oxygen deficiency in shallow areas
Authors: Safonova Kseniia , Meier H. E. Markus , Gröger Matthias
Published: February 2024

Since the early 1980ies, the shallow and brackish Baltic Sea, located in northern Europe, has warmed fastest of all the world’s coastal seas. Hence, the total heat exposure during marine heatwaves increased in frequency and duration, which may have a major impact on the marine ecosystem. We found that marine heatwaves, using two different, commonly used definitions, occurred everywhere on the sea surface since the early 1990s. Periods with sea surface temperatures larger than 20 °C lasting longer than 10 days were particularly numerous in the shallow coastal zone of the southern and eastern Baltic Sea. Furthermore, summer marine heatwaves that reached the seabed mainly occurred in water depths of less than 20 m, where they led to a decrease in oxygen concentration. Since the early 1990s, a positive trend in the expansion of marine heatwaves has been observed on the seabed. The increasing number of marine heatwaves increases the risk of hypoxia events in the coastal zone.
Programmable DNA barcode-encoded exponential amplification reaction for the multiplex detection of miRNAs
Authors: Tan Yuqian , Zhang Li , Deng Shixiong
Published: February 2024

Multiple analysis of miRNAs is essential for the early diagnosis and monitoring of diseases.
A novel β-cyclodextrin-assisted enhancement strategy for portable and sensitive detection of miR-21 in human serum
Authors: Yao Feng , Wu Longjie , Xiong Yamin , Su Chaojie , Guo Yujing , Bulale Shajidan , Zhou Miaomiao , Tian Yongmei , He Leiliang
Published: February 2024

This paper reports improved miR-21 detection signals based on a PGM combined with probe self-assembly and β-CD. The novel biosensor has been successfully applied to detect miR-21 in serum samples.
Computational insights into the zeolite-supported gold nanocluster-catalyzed ethanol dehydrogenation to acetaldehyde
Authors: Zhang Yi , Tang Kangjian , Bao Xiaoguang
Published: February 2024

Herein, computational studies were carried out to gain mechanistic insights into the ethanol dehydrogenation to acetaldehyde under both aerobic and anaerobic conditions catalyzed by silicalite-1 zeolite-encapsulated Au3 cluster cation.
Correlating concerted cations with oxygen redox in rechargeable batteries
Authors: Wang Shiqi , Wang Lifan , Sandoval David , Liu Tongchao , Zhan Chun , Amine Khalil
Published: February 2024

This review underscores the critical importance of oxygen redox and elucidates the precise commonalities of cations in regulating oxygen redox.
Highly efficient photosynthesis of hydrogen peroxide by a stable Zr(iv)-based MOF with a diamino-functionalized ligand
Authors: Zhai Qixiang , Ren Yanwei , Wang Haosen , Liu Cheng , Li Ze , Jiang Huanfeng
Published: February 2024

The introduction of diamino groups into UiO-67 enhances its ability to absorb visible light and facilitates the separation of photogenerated electron/hole pairs, leading to higher photocatalytic activity for H2O2 production from H2O and O2.
In situ grown Bi2WO6@CoMoO4 layered cladding structure on carbon nanofibers by a two-step solvothermal method and Ti mesh substrate as advanced counter electrodes for dye-sensitized solar cells
Authors: Zhang Xiaoyu , Peng Xueyan , Wang Xuan , Zhang Qian , Wang Zixin , Li Ling
Published: February 2024

The electrochemical performance was significantly enhanced by CNFs@Bi2WO6@CoMoO4 layered structure, and the as-assembled dye-sensitized solar cells (DSSCs) delivered an impressive power conversion efficiency of 9.41% at AM 1.5G.
Strain and collapse during lithiation of layered transition metal oxides: a unified picture
Authors: Jousseaume Thibaut , Colin Jean-François , Chandesris Marion , Lyonnard Sandrine , Tardif Samuel
Published: February 2024

Developing long-life, high-energy density materials such as the Ni-rich LiNixMnyCozO2 (NMCxyz) is needed to manufacture advanced Li-ion batteries.
Co-transport of ferrihydrite–organic matter colloids with Sb(v) in saturated porous media: implications for antimony mobility
Authors: Mao Wenjian , Wang Dengjun , Wu Pan , Zhu Jian , Liao Peng , Lai Kaidi , Ding Zihan , Zhang Yuqin , He Zhongxu , Zheng Ruyi , Chen Yonglin
Published: February 2024

Schematic diagram of the mechanism of Fe–NOM–Sb(v) colloids formation and transport in the natural environment.
Blockade of exosome release alleviates the hypersensitive reaction by influencing the T helper cell population in cow's milk allergic mice
Authors: Ma Xin , Xia Jiaheng , Yuan Jin , Meng Xuanyi , Chen Hongbing , Li Xin
Published: February 2024

Exosomes are involved in the immune response of cow's milk allergy and the inhibition of exosome release with GW4869 reversed the allergic reaction by altering the Th population of splenocytes.
Tonicity-induced cargo loading into extracellular vesicles
Authors: Lee Chaeeun , Kumar Sumit , Park Juhee , Choi Yongjun , Clarissa Elizabeth Maria , Cho Yoon-Kyoung
Published: February 2024

Tonicity-induced cargo loading into extracellular vesicles (EVs) is achieved through controlled membrane permeability, ensuring cargo incorporation without causing damage to the EV membrane.
4D printed biocompatible magnetic nanocomposites toward deployable constructs
Authors: Choudhury Saswat , Joshi Akshat , Dasgupta Debayan , Ghosh Ambarish , Asthana Sonal , Chatterjee Kaushik
Published: February 2024

Herein, an alternating magnetic field-triggered shape memory polymer composite has been 3D printed as a tissue scaffold that can be remotely deployed at physiological temperatures and can be extended to soft robotics.
The medicinal chemistry evolution of antibody–drug conjugates
Authors: Hobson Adrian D.
Published: February 2024

For an optimal ADC the symbiotic relationship of the three structurally disparate components requires they all function in unison and medicinal chemistry has a huge role to enable this.
Two-dimensional topological semimetals: an emerging candidate for terahertz detectors and on-chip integration
Authors: Li Yun , Yu Wenzhi , Zhang Kai , Cui Nan , Yun Tinghe , Xia Xue , Jiang Yan , Zhang Guangyu , Mu Haoran , Lin Shenghuang
Published: February 2024

This review presents current research on semimetal-based terahertz detectors and explores their potential for miniaturization and integration.
The role of surface functionalization in quantum dot-based photocatalytic CO2 reduction: balancing efficiency and stability
Authors: Hernandez Frida , Yang Maggie , Nagelj Nejc , Lee Autumn Y. , Noh Hasun , Hur Kyle P. , Fu Xinyu , Savoie Caleb J. , Schwartzberg Adam M. , Olshansky Jacob H.
Published: February 2024

Importance of surface functionalization: a strongly interacting quantum dot–catalyst system achieves higher conversion of CO2 to CO.
Rational electrolyte design and electrode regulation for boosting high-capacity Zn-iodine fiber-shaped batteries with four-electron redox reactions
Authors: Wang Jiuqing , Xu Hai , Zhang Ruanye , Sun Gengzhi , Dou Hui , Zhang Xiaogang
Published: February 2024

A novel aqueous Zn-iodine fiber-shaped battery (AZIFB) with a four-electron redox mechanism was fabricated based on 20 m ZnCl2/1 m methyl ammonium iodide electrolyte and graphene fiber cathode, which exhibits high capacity and wearable potential.
Organoboron–thiophene-based polymer electrodes for high-performance lithium-ion batteries
Authors: Bai Yunfei , Liu Ting , Peng Huayu , Zhao Han , Fan Qingchen , Pan Xiaobo , Zhou Lian , Zhao Hao
Published: February 2024

Boron unit stabilized polymer spin system to enhance anode electrochemical performance.
Current status of research on composite bipolar plates for proton exchange membrane fuel cells (PEMFCs): nanofillers and structure optimization
Authors: Wenkai Li , Zhiyong Xie , Haodong Zeng
Published: February 2024

Research progress and analysis of composite bipolar plates for proton exchange membrane fuel cells – nanofillers: carbon black, carbon nanotubes, graphene. Structural optimization: distribution, conductive path and interface modification.
Optimisation of greener and more efficient 1,7-octadiene epoxidation catalysed by a polymer-supported Mo(vi) complex via response surface methodology
Authors: Bhuiyan Md Masud Rana , Saha Basudeb
Published: February 2024

In this study, a greener and more efficient alkene epoxidation process has been developed using a heterogeneous polybenzimidazole supported Mo(vi) catalyst and tert-butyl hydroperoxide (TBHP) as an oxidising reagent.
NIR-triggered logic gate in MXene-modified perovskite resistive random access memory
Authors: Li Rongbin , Sun Yan , Zhao Qianyu , Hao Xin , Liang Haowei , Xu Shengang , Liu Yingliang , Bi Xiaoman , Cao Shaokui
Published: February 2024

The NIR-responsive MXene@MAPbI3-based resistive switching RRAMs at 1064 nm are prepared. They can be applied in integrated data-storing and information-processing, especially in in vivo manually controlled biocompatible microchips.
Mechanical properties of amorphous CO2 hydrates: insights from molecular simulations
Authors: Cao Pinqiang , Wu Jianyang , Ning Fulong
Published: February 2024

Structural evolutions of amorphous hydrates are characterized by an ordering phenomenon, providing molecular insights into understanding physicochemical properties of clathrates.
Synthesis, characterisation and reactivity of a zinc triazenide for potential use in vapour deposition
Authors: Samii Rouzbeh , Barkas Essi , Zanders David , Fransson Anton , Lahtinen Manu , Kessler Vadim , Tuononen Heikki M. , Moilanen Jani O. , O'Brien Nathan J.
Published: February 2024

Herein, we synthesise and characterise a new volatile and thermally stable Zn(ii) triazenide. We also react it with a bulky thiol to give two different Zn(ii) thiolates. This new triazenide shows high promise as a precursor for vapour deposition of ZnS thin films.
Access to long-lived room temperature phosphorescence through auration of 2,1,3-benzothiadiazole
Authors: Posada Urrutia Mauricio , Kaul Nidhi , Kaper Tobias , Hurrell Dustin , Chiang Linus , Wells Jordann A. L. , Orthaber Andreas , Hammarström Leif , Pilarski Lukasz T. , Dyrager Christine
Published: February 2024

A series of 2,1,3-benzothiadiazole–Au(i)–L complexes have been synthesised, structurally characterised and investigated for their photophysical properties.
Activating lattice oxygen based on energy band engineering in oxides for industrial water/saline oxidation
Authors: Zhang Yijie , Zhang Weiyi , Zhang Xiaowen , Wang Xin , Wang Jiajun , Zhao Qiang , Sun Yuhan , Li Jinping , Liu Guang , Han Xiaopeng
Published: February 2024

The oxide energy bands are adjusted by introducing Fe and F ions, thereby activating lattice oxygen for superior electrocatalytic performance.