Challenges in quantifying functional redundancy and selection in microbial communities.

Microbiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grown in vitro are selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.

Resource competition predicts assembly of gut bacterial communities in vitro.

Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual species, growth measurements in spent media and mathematical models. We applied our framework to an in vitro model system comprising 15 human gut commensals in complex media and showed that a simple model of resource competition accounted for most pairwise interactions. Next, we built a coarse-grained consumer-resource model by grouping metabolomic features depleted by the same set of species and showed that this model predicted the composition of 2-member to 15-member communities with reasonable accuracy. Furthermore, we found that incorporation of cross-feeding and pH-mediated interactions improved model predictions of species coexistence. Our theoretical model and experimental framework can be applied to characterize interspecies interactions in bacterial communities in vitro.

Real-World Sensitization and Tolerance Pattern to Seafood in Fish-Allergic Individuals.

BACKGROUND: Seafood is a common cause of food allergy and anaphylaxis, but there are limited published real-world data describing the clinical presentation of fish and shellfish allergies. OBJECTIVE: This study aimed to examine the clinical characteristics, immunological profile, and tolerance pattern to fish, crustaceans, and mollusks in fish-allergic individuals. METHODS: Patients presenting with IgE-mediated fish allergy between 2016 and 2021 were recruited. A comprehensive sensitization profile including specific IgE and skin prick test to various fish and shellfish species and a detailed clinical history including individuals' recent seafood consumption were evaluated. RESULTS: A total of 249 fish-allergic individuals (aged 4.2 ± 5.8 years) were recruited from 6 allergy clinics in Hong Kong, and they had experienced their fish-allergic reaction 2.2 ± 3.4 years before enrollment. Seventy-five subjects (30%) reacted to either grass carp, salmon, grouper, or cod in oral food challenges. We identified an IgE sensitization gradient that corresponded to the level of ß-parvalbumin in fish. In total, 40% of fish-allergic individuals reported tolerance to 1 or more types of fish, more commonly to fish with a lower ß-parvalbumin level such as tuna and salmon, compared with ß-parvalbumin-rich fish such as catfish and grass carp. Despite fish and shellfish cosensitization, 41% of individuals reported tolerance to crustaceans, mollusks, or both, whereas shellfish avoidance occurred in half of the fish-allergic individuals, of whom 33% lacked shellfish sensitization. CONCLUSIONS: Fish allergy commonly presents in early childhood. A considerable proportion of fish-allergic patients are selectively tolerant to certain fish, typically those with lower levels of ß-parvalbumin. There is an unmet need to promote precision medicine for seafood allergies.

An AIE-active bacterial inhibitor and photosensitizer for selective imaging, killing, and photodynamic inactivation of bacteria over mammalian cells.

Photodynamic therapy is becoming increasingly popular for combat of bacteria. In the clinical photodynamic combat of bacteria, one critical issue is to avoid the potential damage to the host since the reactive oxygen species produced by photosensitizers are also harmful to mammalian cells. In this work, we report an aggregation-induced-emission-active bacterial inhibitor and photosensitizer, OEO-TPE-MEM (OTM), for the imaging, killing, and light-enhanced inactivation of bacteria. OTM could efficiently bind to and kill Gram-positive bacteria, while its affinity to Gram-negative bacteria is lower, and a higher OTM concentration is required for killing Gram-negative bacteria. OTM is also an efficient photosensitizer and could efficiently sensitize the production of reactive oxygen species, which enhances its killing effect on both Gram-positive and Gram-negative bacteria. More interestingly, OTM is very biocompatible with normal mammalian cells both in the dark and under light irradiation. OTM in mice models with bacteria-infected wounds could promote the healing of infected wounds without affecting their organs and blood parameters, which makes it an excellent candidate for clinical applications.

High-Performance WSe2 Top-Gate Devices with Strong Spacer Doping.

Because of the lack of contact and spacer doping techniques for two-dimensional (2D) transistors, most high-performance 2D devices have been produced with nontypical structures that contain electrical gating in the contact regions. In the present study, we used chloroauric acid (HAuCl4) as a strong p-dopant for WSe2 monolayers used in transistors. The HAuCl4-doped devices exhibited a record-low contact resistance of 0.7 kΩ·µm under a doping concentration of 1.76 × 1013 cm-2. In addition, an extrinsic carrier diffusion phenomenon was discovered in the HAuCl4-WSe2 system. With a suitably designed spacer length for doping, a normally off, high-performance underlap top-gate device can be produced without the application of additional gating in the contact and spacer regions.

High-Performance Two-Dimensional Electronics with a Noncontact Remote Doping Method.

Because of the intrinsic low carrier density of monolayer two-dimensional (2D) materials, doping is crucial for the performance of underlap top-gated 2D devices. However, wet etching of a high-k (dielectric constant) dielectric layer is difficult to implement without causing performance deterioration on the devices; therefore, finding a suitable spacer doping technique for 2D devices is indispensable. In this study, we developed a remote doping (RD) method in which defective SiOx can remotely dope the underlying high-k capped 2D regions without directly contacting these materials. This method achieved a doping density as high as 1.4 × 1013 cm-2 without reducing the mobility of the doped materials; after 1 month, the doping concentration remained as high as 1.2 × 1013 cm-2. Defective SiOx can be used to dope most popular 2D transition-metal dichalcogenides. The low-k properties of SiOx render it ideal for spacer doping, which is very attractive from the perspective of circuit operation. In our experiments, MoS2 and WS2 underlap top-gate devices exhibited 10× and 200× increases in their on-currents, respectively, after being doped with SiOx. These results indicate that SiOx doping can be conducted to manufacture high-performance 2D devices.

Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

Modulation of antibiotic effects on microbial communities by resource competition.

Antibiotic treatment significantly impacts the human gut microbiota, but quantitative understanding of how antibiotics affect community diversity is lacking. Here, we build on classical ecological models of resource competition to investigate community responses to species-specific death rates, as induced by antibiotic activity or other growth-inhibiting factors such as bacteriophages. Our analyses highlight the complex dependence of species coexistence that can arise from the interplay of resource competition and antibiotic activity, independent of other biological mechanisms. In particular, we identify resource competition structures that cause richness to depend on the order of sequential application of antibiotics (non-transitivity), and the emergence of synergistic and antagonistic effects under simultaneous application of multiple antibiotics (non-additivity). These complex behaviors can be prevalent, especially when generalist consumers are targeted. Communities can be prone to either synergism or antagonism, but typically not both, and antagonism is more common. Furthermore, we identify a striking overlap in competition structures that lead to non-transitivity during antibiotic sequences and those that lead to non-additivity during antibiotic combination. In sum, our results establish a broadly applicable framework for predicting microbial community dynamics under deleterious perturbations.

Recent Advances in Metal Complexes for Antimicrobial Photodynamic Therapy.

Antimicrobial resistance (AMR) is a growing global problem with more than 1 million deaths due to AMR infection in 2019 alone. New and innovative therapeutics are required to overcome this challenge. Antimicrobial photodynamic therapy (aPDT) is a rapidly growing area of research poised to provide much needed help in the fight against AMR. aPDT works by administering a photosensitizer (PS) that is activated only when irradiated with light, allowing high spatiotemporal control and selectivity. The PS typically generates reactive oxygen species (ROS), which can damage a variety of key biological targets, potentially circumventing existing resistance mechanisms. Metal complexes are well known to display excellent optoelectronic properties, and recent focus has begun to shift towards their application in tackling microbial infections. Herein, we review the last five years of progress in the emerging field of small-molecule metal complex PSs for aPDT.

A dual organelle-targeting mechanosensitive probe.

Cells are responsive to the mechanical environment, but the methods to detect simultaneously how different organelles react in mechanobiological processes remain largely unexplored. We herein report a dual organelle-targeting fluorescent probe, (E)-1-[3-(diethoxyphosphoryl)propyl]-4-[4-(diethylamino)styryl]pyridin-1-ium bromide (ASP-PE), for mechanical mapping in live cells. ASP-PE is aggregation-induced emission active and is sensitive to the local mechanical environment. It targets the plasma membrane (PM) and intracellular mitochondria in cells by its phosphonate moiety and pyridinium. In this work, through ASP-PE staining, changes of membrane tension in the PM and mitochondria in response to varied osmotic pressure and substrate stiffness are visualized using fluorescence lifetime imaging microscopy. The mechanobiological importance of actin filaments and microtubules in the PM and mitochondria is also investigated using this probe. Computational simulations are applied to study the sensing mechanism of the probe. This study introduces a unique tool for mapping the membrane tension in the PM and mitochondria together, providing us great opportunities to study organelle's interactions in mechanobiology.

Assembly of gut-derived bacterial communities follows "early-bird" resource utilization dynamics.

Diet can impact host health through changes to the gut microbiota, yet we lack mechanistic understanding linking nutrient availability and microbiota composition. Here, we use thousands of microbial communities cultured in vitro from human feces to uncover simple assembly rules and develop a predictive model of community composition upon addition of single nutrients from central carbon metabolism to a complex medium. Community membership was largely determined by the donor feces, whereas relative abundances were determined by the supplemental carbon source. The absolute abundance of most taxa was independent of the supplementing nutrient, due to the ability of fast-growing organisms to quickly exhaust their niche in the complex medium and then exploit and monopolize the supplemental carbon source. Relative abundances of dominant taxa could be predicted from the nutritional preferences and growth dynamics of species in isolation, and exceptions were consistent with strain-level variation in growth capabilities. Our study reveals that community assembly follows simple rules of nutrient utilization dynamics and provides a predictive framework for manipulating gut commensal communities through nutritional perturbations.

Hysteresis-Free Contact Doping for High-Performance Two-Dimensional Electronics.

Contact doping is considered crucial for reducing the contact resistance of two-dimensional (2D) transistors. However, a process for achieving robust contact doping for 2D electronics is lacking. Here, we developed a two-step doping method for effectively doping 2D materials through a defect-repairing process. The method achieves strong and hysteresis-free doping and is suitable for use with the most widely used transition-metal dichalcogenides. Through our method, we achieved a record-high sheet conductance (0.16 mS·sq-1 without gating) of monolayer MoS2 and a high mobility and carrier concentration (4.1 × 1013 cm-2). We employed our robust method for the successful contact doping of a monolayer MoS2 Au-contact device, obtaining a contact resistance as low as 1.2 kΩ·µm. Our method represents an effective means of fabricating high-performance 2D transistors.

Design, construction, and in vivo augmentation of a complex gut microbiome.

Efforts to model the human gut microbiome in mice have led to important insights into the mechanisms of host-microbe interactions. However, the model communities studied to date have been defined or complex, but not both, limiting their utility. Here, we construct and characterize in vitro a defined community of 104 bacterial species composed of the most common taxa from the human gut microbiota (hCom1). We then used an iterative experimental process to fill open niches: germ-free mice were colonized with hCom1 and then challenged with a human fecal sample. We identified new species that engrafted following fecal challenge and added them to hCom1, yielding hCom2. In gnotobiotic mice, hCom2 exhibited increased stability to fecal challenge and robust colonization resistance against pathogenic Escherichia coli. Mice colonized by either hCom2 or a human fecal community are phenotypically similar, suggesting that this consortium will enable a mechanistic interrogation of species and genes on microbiome-associated phenotypes.

Mothers' caregiving during COVID: The impact of marital property laws on women's labor force status.

If mothers take care of children more than fathers, then after the onset of COVID-19 mothers' employment is expected to drop more than that of fathers. This gender gap is likely to be larger where women are less concerned about the financial repercussions of opting out of the labor force, and therefore the gender gap in employment is likely to grow more where community property or homemaking provisions give more protection to homemakers in case of union dissolution. Difference-in-differences and dynamic study estimations applied to CPS data for 2019-2020 show that after the onset of COVID-19 the labor force participation of mothers of school-age children-but not of fathers--dropped more in states with marital property laws more generous to parental caregivers. These results stand in contrast to how these groups' labor force participation changed after the Great Recession, compared to pre-recession levels.

Electrically Driven Hyperbolic Nanophotonic Resonators as High Speed, Spectrally Selective Thermal Radiators.

We introduce and experimentally demonstrate electrically driven, spectrally selective thermal emitters based on globally aligned carbon nanotube metamaterials. The self-assembled metamaterial supports a high degree of nanotube ordering, enabling nanoscale ribbons patterned in the metamaterial to function both as Joule-heated incandescent filaments and as infrared hyperbolic resonators imparting spectral selectivity to the thermal radiation. Devices batch-fabricated on a single chip emit polarized thermal radiation with peak wavelengths dictated by their hyperbolic resonances, and their nanoscale heated dimensions yield modulation rates as high as 1 MHz. As a proof of concept, we show that two sets of thermal emitters on the same chip, operating with different peak wavelengths and modulation rates, can be used to sense carbon dioxide with one detector. We anticipate that the combination of batch fabrication, modulation bandwidth, and spectral tuning with chip-based nanotube thermal emitters will enable new modalities in multiplexed infrared sources.

Replica of Bionic Nepenthes Peristome-like and Anti-Fouling Structures for Self-Driving Water and Raman-Enhancing Detection.

The flexible, anti-fouling, and bionic surface-enhanced Raman scattering (SERS) biochip, which has a Nepenthes peristome-like structure, was fabricated by photolithography, replicated technology, and thermal evaporation. The pattern of the bionic Nepenthes peristome-like structure was fabricated by two layers of photolithography with SU-8 photoresist. The bionic structure was then replicated by polydimethylsiloxane (PDMS) and grafting the zwitterion polymers (2-methacryloyloxyethyl phosphorylcholine, MPC) by atmospheric plasma polymerization (PDMS-PMPC). The phospholipid monomer of MPC immobilization plays an important role; it can not only improve hydrophilicity, anti-fouling and anti-bacterial properties, and biocompatibility, but it also allows for self-driving and unidirectional water delivery. Ag nanofilms (5 nm) were deposited on a PDMS (PDMS-Ag) substrate by thermal evaporation for SERS detection. Characterizations of the bionic SERS chips were measured by a scanning electron microscope (SEM), optical microscope (OM), X-ray photoelectron spectrometer (XPS), Fourier-transform infrared spectroscopy (FTIR), and contact angle (CA) testing. The results show that the superior anti-fouling capability of proteins and bacteria (E. coli) was found on the PDMS-PMPC substrate. Furthermore, the one-way liquid transfer capability of the bionic SERS chip was successfully demonstrated, which provides for the ability to separate samples during the flow channel, and which was detected by Raman spectroscopy. The SERS intensity (adenine, 10-4 M) of PDMS-Ag with a bionic structure is ~4 times higher than PDMS-Ag without a bionic structure, due to the multi-reflection of the 3D bionic structure. The high-sensitivity bionic SERS substrate, with its self-driving water capability, has potential for biomolecule separation and detection.

Coping resources mediate the prospective associations between disrupted daily routines and persistent psychiatric symptoms: A population-based cohort study.

This study examined the mediating effects of coping resources in the prospective associations between daily routine disruptions in the acute phase of COVID-19 and persistent probable anxiety and depression. A prospective, population-representative cohort of 1318 Hong Kong Chinese respondents completed a baseline survey between February and July 2020 (T1) and a 1-year follow-up survey between March and August 2021 (T2). Respondents reported demographics and disruptions to primary and secondary daily routines at T1, coping resources (i.e., self-efficacy and meaning making) at T2, and anxiety and depressive symptoms at T1 and T2. We found that 8.1% and 10.0% of respondents reached cutoff scores for probable anxiety and depression respectively at both T1 and T2. Logistic regression showed that T1 daily routine disruptions were positively associated with heightened risk of persistent probable anxiety and depression amid COVID-19. Path analysis showed that 15.3% and 13.1% of the associations of daily routine disruptions with persistent probable anxiety and depression were explained by coping resources, respectively, while the direct routine-outcome associations remained significant. Daily routine disruptions predict higher odds of persistent probable anxiety and depression directly and partially through reducing coping resources. Sustainment of regular daily routines should be advocated and fostered to enhance coping resources and reduce the risk of poorer adjustment among the affected populations amid public health crises.

Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy.

BACKGROUND: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. METHODS: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. RESULTS: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. CONCLUSION: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.

Competition for fluctuating resources reproduces statistics of species abundance over time across wide-ranging microbiotas.

Across diverse microbiotas, species abundances vary in time with distinctive statistical behaviors that appear to generalize across hosts, but the origins and implications of these patterns remain unclear. Here, we show that many of these macroecological patterns can be quantitatively recapitulated by a simple class of consumer-resource models, in which the metabolic capabilities of different species are randomly drawn from a common statistical distribution. Our model parametrizes the consumer-resource properties of a community using only a small number of global parameters, including the total number of resources, typical resource fluctuations over time, and the average overlap in resource-consumption profiles across species. We show that variation in these macroscopic parameters strongly affects the time series statistics generated by the model, and we identify specific sets of global parameters that can recapitulate macroecological patterns across wide-ranging microbiotas, including the human gut, saliva, and vagina, as well as mouse gut and rice, without needing to specify microscopic details of resource consumption. These findings suggest that resource competition may be a dominant driver of community dynamics. Our work unifies numerous time series patterns under a simple model, and provides an accessible framework to infer macroscopic parameters of effective resource competition from longitudinal studies of microbial communities.

Testing a New Protocol of Nature-Based Intervention to Enhance Well-Being: A Randomized Control Trial.

This study aims to test the associations of nature contact with multiple dimensions of psychological functioning. A total of 90 university employees were randomly assigned to spend their lunch breaks on (1) a 30-min structured protocol of nature contact and (2) a control group for 10 consecutive weekdays. Psychological distress, psychological well-being, and work-related psychological outcomes were assessed at baseline (T1), the day after the 10-day intervention (T2), and three months after the intervention (T3). Mixed-design analyses of variance (ANOVA) were conducted. Overall, significant intervention effects were found in the structured protocol of nature contact on psychological distress, well-being outcomes, and work engagement (all p < 0.05), whereas the 3-month post-intervention effects were non-significant. Our study showed that nature-based activities during lunch breaks could enhance office workers' mental health in general, but the effects could be short-lived, calling for regular nature-based programs in occupational settings.