Momentum-exchange interactions in a Bragg atom interferometer suppress Doppler dephasing.

Large ensembles of laser-cooled atoms interacting through infinite-range photon-mediated interactions are powerful platforms for quantum simulation and sensing. Here we realize momentum-exchange interactions in which pairs of atoms exchange their momentum states by collective emission and absorption of photons from a common cavity mode, a process equivalent to a spin-exchange or XX collective Heisenberg interaction. The momentum-exchange interaction leads to an observed all-to-all Ising-like interaction in a matter-wave interferometer. A many-body energy gap also emerges, effectively binding interferometer matter-wave packets together to suppress Doppler dephasing in analogy to Mössbauer spectroscopy. The tunable momentum-exchange interaction expands the capabilities of quantum interaction-enhanced matter-wave interferometry and may enable the realization of exotic behaviors, including simulations of superconductors and dynamical gauge fields.

SPEED: an integrated, smartphone-operated, handheld digital PCR Device for point-of-care testing.

This study elaborates on the design, fabrication, and data analysis details of SPEED, a recently proposed smartphone-based digital polymerase chain reaction (dPCR) device. The dPCR chips incorporate partition diameters ranging from 50 µm to 5 µm, and these partitions are organized into six distinct blocks to facilitate image processing. Due to the superior thermal conductivity of Si and its potential for mass production, the dPCR chips were fabricated on a Si substrate. A temperature control system based on a high-power density Peltier element and a preheating/cooling PCR protocol user interface shortening the thermal cycle time. The optical design employs four 470 nm light-emitting diodes as light sources, with filters and mirrors effectively managing the light emitted during PCR. An algorithm is utilized for image processing and illumination nonuniformity correction including conversion to a monochromatic format, partition identification, skew correction, and the generation of an image correction mask. We validated the device using a range of deoxyribonucleic acid targets, demonstrating its potential applicability across multiple fields. Therefore, we provide guidance and verification of the design and testing of the recently proposed SPEED device.

An integrated microfluidic platform for nucleic acid testing.

This study presents a rapid and versatile low-cost sample-to-answer system for SARS-CoV-2 diagnostics. The system integrates the extraction and purification of nucleic acids, followed by amplification via either reverse transcription-quantitative polymerase chain reaction (RT-qPCR) or reverse transcription loop-mediated isothermal amplification (RT-LAMP). By meeting diverse diagnostic and reagent needs, the platform yields testing results that closely align with those of commercial RT-LAMP and RT‒qPCR systems. Notable advantages of our system include its speed and cost-effectiveness. The assay is completed within 28 min, including sample loading (5 min), ribonucleic acid (RNA) extraction (3 min), and RT-LAMP (20 min). The cost of each assay is ≈ $9.5, and this pricing is competitive against that of Food and Drug Administration (FDA)-approved commercial alternatives. Although some RNA loss during on-chip extraction is observed, the platform maintains a potential limit of detection lower than 297 copies. Portability makes the system particularly useful in environments where centralized laboratories are either unavailable or inconveniently located. Another key feature is the platform's versatility, allowing users to choose between RT‒qPCR or RT‒LAMP tests based on specific requirements.

[Analysis of rare mutations associated with Thalassemia and their hematological characteristics in Chenzhou region of Hunan Province].

OBJECTIVE: To explore the distribution and hematological characteristics of rare thalassemia-associated mutations in Chenzhou region of Hunan Province with an aim to provide a basis for genetic counseling and effective prevention. METHODS: A total of 37 370 individuals enrolled from January 2015 to December 2021 were screened by routine blood test and hemoglobin electrophoresis. The genotypes were determined with high-throughput sequencing. RESULTS: A total of 8 455 thalassemia mutations (including 185 rare ones) were detected, which had involved 27 mutational types. Rare type α-Thalassemia --THAI and CD31 (AGG>AAG) have the typical microcytic hypochromic hematological features, whilst SEA-HPFH, CD14 (CTG>-TG), CD37 (TGG>TAG), -90(C>T), Codon 15 (G>A), IVS-I-128 (T>G), CD86 (GCC>GC-) and Chinese Gγ+(Aγδß)0 had typical microcytic hypochromic and ß-thalassemia-associated hematological features of elevated HbA2 or HbF. In addition, the -50（G>A）heterozygotes of ß-thalassemia had normal or slightly decreased MCV and MCH without an increase in HbA2. CONCLUSION: Various forms of thalassemia-associated mutations have been identified in the Chenzhou region of Hunan Province. Above finding has facilitated development of preventive and control strategies for thalassemia as well as birth health programs.

Synthetic Gene Circuit-Based Assay with Multilevel Switch Enables Background-Free and Absolute Quantification of Circulating Tumor DNA.

Circulating tumor DNA (ctDNA) detection has found widespread applications in tumor diagnostics and treatment, where the key is to obtain accurate quantification of ctDNA. However, this remains challenging due to the issue of background noise associated with existing assays. In this work, we developed a synthetic gene circuit-based assay with multilevel switch (termed CATCH) for background-free and absolute quantification of ctDNA. The multilevel switch combining a small transcription activating RNA and a toehold switch was designed to simultaneously regulate transcription and translation processes in gene circuit to eliminate background noise. Moreover, such a multilevel switch-based gene circuit was integrated with a Cas9 nickase H840A (Cas9n) recognizer and a molecular beacon reporter to form CATCH for ctDNA detection. The CATCH can be implemented in one-pot reaction at 35 °C with virtually no background noise, and achieve robust absolute quantification of ctDNA when integrated with a digital chip (i.e., digital CATCH). Finally, we validated the clinical capability of CATCH by detecting drug-resistant ctDNA mutations from the plasma of 76 non-small cell lung cancer (NSCLC) patients, showing satisfying clinical sensitivity and specificity. We envision that the simple and robust CATCH would be a powerful tool for next-generation ctDNA detection.

Application of microfluidic technologies in forensic analysis.

The application of microfluidic technology in forensic medicine has steadily expanded over the last two decades due to the favorable features of low cost, rapidity, high throughput, user-friendliness, contamination-free, and minimum sample and reagent consumption. In this context, bibliometric methods were adopted to visualize the literature information contained in the Science Citation Index Expanded from 1989 to 2022, focusing on the co-occurrence analysis of forensic and microfluidic topics. A deep interpretation of the literature was conducted based on co-occurrence results, in which microfluidic technologies and their applications in forensic medicine, particularly forensic genetics, were elaborated. The purpose of this review is to provide an impartial evaluation of the utilization of microfluidic technology in forensic medicine. Additionally, the challenges and future trends of implementing microfluidic technology in forensic genetics are also addressed.

[The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. METHODS: 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. RESULTS: Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). CONCLUSION: NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

[Diagnostic value of whole exome sequencing for patients with intellectual disability or global developmental delay].

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for patients with intellectual disability (ID) or global developmental delay (GDD). METHODS: 134 individuals with ID or GDD who presented at Chenzhou First People's Hospital between May 2018 and December 2021 were selected as the study subjects. WES was carried out on peripheral blood samples of the patients and their parents, and candidate variants were verified by Sanger sequencing, copy number variation sequencing (CNV-seq) and co-segregation analysis. The pathogenicity of the variants was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: A total of 46 pathogenic single nucleotide variants (SNVs) and small insertion/deletion (InDel) variants, 11 pathogenic genomic copy number variants (CNVs), and 1 uniparental diploidy (UPD) were detected, which yielded an overall detection rate of 43.28% (58/134). The 46 pathogenic SNV/InDel have involved 62 mutation sites in 40 genes, among which MECP2 was the most frequent (n = 4). The 11 pathogenic CNVs have included 10 deletions and 1 duplication, which have ranged from 0.76 to 15.02 Mb. A loss of heterozygosity (LOH) region of approximately 15.62 Mb was detected in 15q11.2q12 region in a patient, which was validated as paternal UPD based on the result of trio-WES. The patient was ultimately diagnosed as Angelman syndrome. CONCLUSION: WES can detect not only SNV/InDel, but also CNV and LOH. By integrating family data, WES can accurately determine the origin of the variants and provide a useful tool for uncovering the genetic etiology of patients with ID or GDD.

A three-in-one microfluidic droplet digital PCR platform for absolute quantitative analysis of DNA.

Droplet digital polymerase chain reaction (ddPCR) technology has found widespread applications in the ultrasensitive analysis of nucleic acids, where integrated ddPCR platforms with the capability of sample dispersion, followed by in situ amplification and data analysis, are highly expected. However, current integrated ddPCR platforms are usually limited by either difficultly mass-produced materials or lack of integrated control instruments, restricting their practical application. This paper proposes an integrated three-in-one ddPCR platform with high user-friendliness and practicability, which is composed of an easy-to-use chip and a matching control instrument. The chip was made of thermally resistant and easily mass-produced polycarbonate (PC) material, and the benchtop control instrument was designed to perform droplet generation, in situ amplification, and fluorescence reading. The droplet generation and in situ heating on the chip were well characterized. Finally, the performance of the platform was validated through the analysis of the EGFR L858R mutation in lung cancer. The proposed three-in-one ddPCR platform shows great practicability in ultrasensitive nucleic acid testing. By virtue of its sensitivity, practicability, and cost-effectiveness, the ddPCR can serve as a universal detection platform for monitoring nucleic acid in the fields of tumor diagnosis, pathogen detection, and prenatal diagnosis.

Smartphone integrated handheld (SPEED) digital polymerase chain reaction device.

We demonstrate a smartphone integrated handheld (SPEED) digital polymerase chain reaction (dPCR) device for point-of-care application. The device has dimensions of ≈100 × 200 × 35 mm3 and a weight of ≈400 g. It can perform 45 PCR cycles in ≈49 min. The device also features integrated, miniaturized modules for thermal cycling, image taking, and wireless data communication. These functions are controlled by self-developed Android-based applications. The only consumable is the developed silicon-based dPCR chip, which has the potential to be recycled. The device's precision and accuracy are comparable with commercial dPCR machines. We have verified the SPEED dPCR prototype's utility in the testing of severe acute respiratory syndrome coronavirus 2, the detection of cancer-associated gene sequences, and the confirmations of Down syndrome diagnoses. Due to its low upfront capital investment, as well as its nominal running cost, we envision that the SPEED dPCR device will help to perform cancer screenings and non-invasive prenatal tests for the general population. It will also aid in the timely identification and monitoring of infectious disease testing, thereby expediting alerts with respect to potential emerging pandemics.

Baicalin Relieves LPS-Induced Lung Inflammation via the NF-κB and MAPK Pathways.

Baicalin is an active ingredient extracted from the Chinese medicine Scutellaria and has many beneficial effects. Pulmonary interstitial and alveolar edema are common symptoms of an acute lung injury (ALI). We investigated the effects of baicalin on LPS-induced inflammation and the underlying mechanisms in mice and cells. The protein contents and mRNA expression of TNF-α, IL-1ß, and IL-6 in RAW264.7 cells and mice were detected using ELISA and qRT-PCR. Baicalin significantly suppressed TNF-α, IL-1ß, and IL-6 levels and expression, both in vitro and in vivo, compared with the LPS group. Baicalin inhibits the expression of TLR4 and MyD88, resulting in significant decreases in p-p65, p-p38, p-ERK, and p-JNK, as measured by the Western blotting of RAW264.7 cells. A baicalin treatment for 12 h resulted in a rapid increasing of the white blood cell number and significantly improved the pathological changes in the lung. We also found that the baicalin pretreatment for 12 h could decrease the MPO content and wet/dry (W/D) weight ratio, which indicates that baicalin can significantly reduce pulmonary edema. Furthermore, the baicalin pretreatment also resulted in the recovery of TGF-ß protein levels and decreased iNOS. Baicalin inhibits ALI inflammation in mice and cells and is a potential candidate for the treatment of ALI.

Realization of exceptional points along a synthetic orbital angular momentum dimension.

Exceptional points (EPs), at which more than one eigenvalue and eigenvector coalesce, are unique spectral features of non-Hermiticity (NH) systems. They exist widely in open systems with complex energy spectra. We experimentally demonstrate the appearance of paired EPs in a periodical-driven degenerate optical cavity along the synthetic orbital angular momentum dimension with a tunable parameter. The complex-energy band structures and the key features of EPs, i.e., their bulk Fermi arcs, parity-time symmetry breaking transition, energy swapping, and half-integer band windings, are directly observed by detecting the wavefront angle-resolved transmission spectrum. Our results demonstrate the flexibility of using the photonic synthetic dimensions to implement NH systems beyond their geometric dimension and EP-based sensing.

Digital polymerase chain reaction duplexing method in a single fluorescence channel.

The digital polymerase chain reaction (dPCR) technique can quantify specific sequences of deoxyribonucleic acid using either a droplet-based or chip-based system. dPCR duplexing methods in a single fluorescence channel are typically based on the difference in fluorescence amplitude (F) between two targets. The different targets are distinguished from each other by the F-value variation using non-equal probe concentrations or different target lengths. In the present study, we propose a single fluorescence channel-based dPCR duplexing method that combines a specific probe and intercalating dye to increase the difference in F values between the two targets. We selected two sequences, one from chromosome 18 (Chr18) detected only by the intercalating dye EvaGreen and the other from chromosome 21 (Chr21) detected by a combination of a 6-carboxyfluorescein (FAM) probe and EvaGreen. We performed the dPCR protocol and imaged the dPCR chip at room temperature to verify the proposed duplexing method. The result revealed that the difference in F values between Chr18 and Chr21 increased from ≈5% to 20% when using the FAM probe for Chr21 compared with the detection of both amplicons using EvaGreen only. The added FAM probe enabled two-target discrimination using a single-color fluorescent channel. We further determined the difference in F values at different temperatures using artificial dPCR images. This proposed method represents a simple option for single fluorescence channel dPCR duplexing, making it suitable for simplified dPCR systems used for point-of-care applications.

Nitrogen fertilization modulates rice seed endophytic microbiomes and grain quality.

The intensive use of chemical fertilizer, particularly nitrogen (N) has resulted in not only markedly increased crop yields but also detrimental effects on ecosystems. Plant microbiomes represent an eco-friendly alternative for plant nutrition and productivity, and the effect of N fertilization on plant and soil microbes has been well studied. However, if and how N fertilization modulates seed endophytic microbiomes and grain quality remains largely unknown. Here, we investigated the effect of different N fertilization rates on rice seed endophytic bacterial and fungal communities as well as on grain quality. Higher bacterial and fungal community diversity and richness, but lower grain protein and amino acid contents were found in seeds of rice treated moderate N fertilization than those treated insufficient or excessive N input. There were also more complex co-occurrence networks, and an enrichment of putative beneficial bacterial taxa in seeds under moderate N application, while there was an opposite trend under the excessive N treatment. In addition, the grain amylose and amylopectin contents were positively correlated with the relative abundance of bacterial and fungal dominant genera, while the grain amino acid contents were negatively correlated with the bacterial dominant genera but positively associated with fungal dominant genera. Together, we demonstrate that moderate N fertilization can enhance bacterial and fungal community colonization in seeds and improve grain eating and cooking qualities. This study extends our knowledge regarding the significant role of rational fertilization on seed-microbe interactions in sustainable agriculture.

[Distribution of variants of 88 recessive genetic disease-related genes among 1314 individuals from Chenzhou, China].

OBJECTIVE: To determine the carrier rate for common recessive genetic diseases in Chenzhou region in order to provide a reference for carrier screening in this region. METHODS: Targeted capture and high-throughput sequencing were carried out to detect potential variants of 79 genes associated with 88 recessive genetic diseases. Couples at risk were provided with prenatal diagnosis upon their subsequent pregnancies. RESULTS: A total of 1314 individuals were enrolled, among whom 355 (27.02%) were found to be carrier for at least one disease. The carrier rates for 8 diseases have exceeded 1%, with the most common two including thalassemia (11.72%, 154/1314) and autosomal recessive deafness (5.48%, 72/1314). Ten couples were found to be at risk for producing affected offspring. Among these, five females were carriers for X-linked recessive genetic diseases. Following genetic counseling, seven couples had accepted prenatal diagnosis, and 3 affected fetuses were diagnosed. CONCLUSION: The disease types and pathogenic variants of Chenzhou region have differed from previously reported. Further research is required to validate the above finding with a larger populations.

Changes in soil fungal communities after onset of wheat yellow mosaic virus disease.

Rhizosphere-associated microbes have important implications for plant health, but knowledge of the association between the pathological conditions of soil-borne virus-infected wheat and soil microbial communities, especially changes in fungal communities, remains limited. We investigated the succession of fungal communities from bulk soil to wheat rhizosphere soil in both infected and healthy plants using amplicon sequencing methods, and assessed their potential role in plant health. The results showed that the diversity of fungi in wheat rhizosphere and bulk soils significantly differed post wheat yellow mosaic virus disease onset. The structure differences in fungal community at the two wheat health states or two compartment niches were evident, soil physicochemical properties (i.e., NH4 +) contribute to differences in fungal community structure and alpha diversity. Comparison analysis showed Mortierellomycetes and Dothideomycetes as dominant communities in healthy wheat soils at class level. The genus Pyronemataceae and Solicoccozyma were significantly are significantly enriched in rhizosphere soil of diseased plant, the genus Cystofilobasidium, Cladosporium, Mortierella, and Stephanonectria are significantly enriched in bulk soil of healthy plant. Co-occurrence network analysis showed that the fungi in healthy wheat soil has higher mutual benefit and connectivity compared with diseased wheat. The results of this study demonstrated that the occurrence of wheat yellow mosaic virus diseases altered both fungal community diversity and composition, and that NH4 + is the most important soil physicochemical factor influencing fungal diversity and community composition.

Effective modification of photocatalytic and piezocatalytic performances for poly(heptazine imide) by carbon dots decoration.

As the high-crystalline phase of carbon nitride, poly(heptazine imide) (PHI) has attracted much attention in recent years, considering the more effective light absorption, better charge carrier behavior, and higher surface area of PHI compared with its counterpart with a melon structure that is commonly synthesized through thermal polymerization. Nevertheless, exploring effective strategies to further improve the performance of PHI is still highly desirable. In this work, it is revealed that the photocatalytic as well as piezocatalytic performances of PHI are greatly promoted by coupling with carbon dots (CDots) through a facile ultrasonication process. Detailed structure characterizations indicate that a very low content of CDots (0.05%) decoration can double the light absorbance and achieve the efficient separation and transfer of photogenerated charge carriers. The optimal photocatalytic hydrogen evolution rate of PHI/CDots is about 2.49 and 2.81 times that of PHI, under UV-Visible and visible light irradiation, respectively. Moreover, the piezocatalytic H2O2 generation and KMnO4 degradation activities of PHI/CDots are around 2 times that of PHI. The results obtained in this work provide references for the modification of PHI and may inspire new strategies for the design of highly efficient carbonaceous photocatalysts.

Characterization of the belowground microbial community and co-occurrence networks of tobacco plants infected with bacterial wilt disease.

Characterizing the microbial communities associated with soil-borne disease incidence is a key approach in understanding the potential role of microbes in protecting crops from pathogens. In this study, we compared the soil properties and microbial composition of the rhizosphere soil and roots of healthy and bacterial wilt-infected tobacco plants to assess their potential influence on plant health. Our results revealed that the relative abundance of pathogens was higher in diseased plants than in healthy plants. Moreover, compared with healthy plants, there was a significantly higher microbial alpha diversity in the roots and rhizosphere soil of diseased plants. In addition, we detected a lower abundance of certain plant microbiota, including species in the genera Penicillium, Trichoderma, and Burkholderia in the rhizosphere of diseased plants, which were found to be significantly negatively associated with the relative abundance of Ralstonia. Indeed, compared with healthy plants, the co-occurrence networks of diseased plants included a larger number of associations linked to plant health. Furthermore, structural equation modeling revealed that these specific microbes were correlated with disease suppression, thereby implying that they may play important roles in maintaining plant health. In conclusion, our findings provide important insights into the relationships between soil-borne disease incidence and changes in the belowground microbial community. These findings will serve as a basis for further research investigating the use of specific plant-associated genera to inhibit soil-borne diseases.

Topological band structure via twisted photons in a degenerate cavity.

Synthetic dimensions based on particles' internal degrees of freedom, such as frequency, spatial modes and arrival time, have attracted significant attention. They offer ideal large-scale lattices to simulate nontrivial topological phenomena. Exploring more synthetic dimensions is one of the paths toward higher dimensional physics. In this work, we design and experimentally control the coupling among synthetic dimensions consisting of the intrinsic photonic orbital angular momentum and spin angular momentum degrees of freedom in a degenerate optical resonant cavity, which generates a periodically driven spin-orbital coupling system. We directly characterize the system's properties, including the density of states, energy band structures and topological windings, through the transmission intensity measurements. Our work demonstrates a mechanism for exploring the spatial modes of twisted photons as the synthetic dimension, which paves the way to design rich topological physics in a highly compact platform.

Molecular recognition between bacterial phosphorothioate DNA and sulfur-binding domain (SBD): competition between the water cage and chalcogen-hydrophobic packet.

Bacterial DNA phosphorothioation (PT) physiologically and stereo-specifically replaces a non-bridging oxygen in a phosphate link with a sulfur atom, which can be recognized by a highly conserved sulfur-binding domain (SBD). Here we conducted thermodynamic integration (TI), molecular dynamics simulation, and quantum chemical calculations to decipher the specific molecular interactions between PT-DNA and SBD in Streptomyces coelicolor type IV restriction enzyme ScoMcrA. The TI-calculated binding affinity of (5'-CCGRp-PSGCCGG-3')2 is larger than that of (5'-CCGGCCGG-3')2 by about 7.4-7.7 kcal mol-1. The binding difference dominantly stems from hydration energy of non-phosphorothioate DNA (9.8-10.6 kcal mol-1) in aqueous solution, despite the persistent preference of 2.6-3.2 kcal mol-1 in the DNA-SBD MD simulations. Furthermore, the quantum chemical calculations reveal an unusual non-covalent interaction in the phosphorothioate-binding scenario, where the PS⋯NP165 chalcogen bond prevails the PS⋯HCß vdW interactions from the adjacent residues H116-R117-Y164-P165-A168. Thus, the chalcogen-hydrophobic interaction pulls PT-DNA into the SBD binding pocket while the water cage pulls a normal DNA molecule out. The synergetic mechanism suggests the special roles of the proline pyrrolidine group in the SBD proteins, consistent with the experimental observations in the X-ray crystallography and structural bioinformatics analysis.