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Purpose: To further explore the influence of genotype, including mutation type and structural domain, on the severity of macular atrophy, we measured the central retinal thickness (CRT) in patients with ABCA4-related retinopathy. Methods: A total of 66 patients were included in the cohort. This was a retrospective investigation. The patients were tested using whole exon sequencing and ophthalmic exams, including slip lamp exams, best-corrected visual acuity, optical coherence tomography, fundus photo, and fundus autofluorescence. Results: In this study, we discovered that mutations on nucleotide binding domains (NBD) lead to less CRT (45.00 ± 25.25μm, 95% CI: 31.54–58.46) had significantly less CRT than the others (89.75 ± 71.17μm, 95% CI: 30.25–149.25, p= 0.032), and could accelerate the rate of CRT decrease. Conclusions: Our study provides new perspectives in the understanding of ABCA4-related retinopathy.

As the marine industry progresses, copper-containing metallic materials that possess both high strength and ductility are demanding. Traditional copper alloys used in marine environment face challenges regarding inadequate strength and corrosion resistance. In the present work, cold rolling and subsequent high-temperature annealing processes were employed to the Cu1.2NiMnFe0.5Cr0.5Al0.2high-entropy alloy. This alloy exhibited remarkable mechanical properties, including a yield strength (YS) of 530 MPa, ultimate tensile strength (UTS) of 913 MPa, and a relatively high fracture elongation (EL) of 37.7%. After subsequent aging treatment at 400 °C, spinodal decomposition occurred within the matrix, leading to enhanced strength. The decomposed microstructure was comprehensively characterized, and the strengthening mechanism was analyzed. Notably, the sample aged for 6 h exhibited a YS of 701 MPa and an EL of 21.8%. The present HEAs exhibit superior mechanical properties compared to traditional copper alloys and other Cu-containing HEAs, when considering both strength and ductility. Furthermore, these alloys demonstrated exceptional corrosion resistance and a favorable copper ion release rate in 3.5 wt% NaCl solution. This work introduces an innovative class of advanced alloys and offers a strategic approach to alloy design for marine applications.

Supplemental Digital Content is Available in the Text.

The fall armyworm, Spodoptera frugiperda(Lepidoptera: Noctuidae), is a cosmopolitan pest that exploits more than 350 host plants, including economically important crops such as corn, cotton and rice. Control of S. frugiperdalargely relies on transgenic crops producing insecticidal proteins from Bacillus thuringiensis(Bt) and spraying synthetic insecticides. Here, we established the susceptibility and diagnostic concentration for 2 Bt toxins and 5 newer insecticides in invasive populations of S. frugiperdafrom southeastern China. Concentrations causing 50% mortality (LC50) in ten field populations sampled in 2022 ranged from 2.13 to 19.29 and 22.43 to 71.12 ng/cm2for Cry1Fa and Vip3Aa, and 0.83 to 5.30, 2.83 to 9.94, 0.04 to 0.23, 4.59 to 8.40, and 1.49 to 6.79 mg/liter for chlorantraniliprole, chlorfenapyr, emamectin benzoate, indoxacarb, and spinosad, respectively. Relative to the susceptible strain YJ-19, the largest resistance ratio in the field populations was 5.1, 1.6, 6.2, 3.9, 4.6, 2.2, and 3.6 for Cry1Fa, Vip3Aa, chlorantraniliprole, chlorfenapyr, emamectin benzoate, indoxacarb, and spinosad, respectively, indicating that the field populations were generally susceptible to these Bt toxins and insecticides. Based on the pooled response of the field populations, the diagnostic concentration for resistance monitoring, estimated as ca. twice the LC99, was 400 and 1,500 ng/cm2for Cry1Fa and Vip3Aa, and 2, 40, 60, 60, and 100 mg/liter for emamectin benzoate, chlorantraniliprole, chlorfenapyr, spinosad, and indoxacarb, respectively. These results provide useful information for monitoring resistance to key Bt toxins and insecticides for the control of S. frugiperdain China.

Leber hereditary optic neuropathy (LHON) is the most common maternally inherited mitochondrial disease, with >90% of cases harboring one of three point variants (m.3460G>A, m.11778G>A, and m.14484T>C). Rapid and sensitive diagnosis of LHON variants is urgently needed for early diagnosis and timely treatment after onset, which is currently limited. Herein, we adapted the Cas12a-based DNA detection platform for LHON mitochondrial variant diagnosis. Single-strand guide CRISPR RNAs and enzymatic recombinase amplification primers were first screened, the CRISPR/Cas12a system was then optimized with restriction enzymes, and finally compared with Sanger sequencing and next-generation sequencing (NGS) in multicenter clinical samples. This approach can be completed within 30 minutes using only one drop of blood and could reach a sensitivity of 1% of heteroplasmy. Among the 182 multicenter clinical samples, the CRISPR/Cas12a detection system showed high consistency with Sanger sequencing and NGS in both specificity and sensitivity. Notably, a sample harboring a de novo3.78% m.11778G>Avariant detected by NGS, but not by Sanger sequencing, was successfully confirmed using the CRISPR/Cas12a assay, which proved the effectiveness of our method. Overall, our CRISPR/Cas12a detection system provides an alternative for rapid, convenient, and sensitive detection of LHON variants, exhibiting great potential for clinical practice.

Crops genetically engineered to produce insect-killing proteins from Bacillus thuringiensis(Bt) have revolutionized management of some major pests, but their efficacy is reduced when pests evolve resistance. Practical resistance, which is field-evolved resistance that reduces the efficacy of Bt crops and has practical implications for pest management, has been reported in 26 cases in seven countries involving 11 pest species. This special collection includes six original papers that present a global perspective on field-evolved resistance to Bt crops. One is a synthetic review providing a comprehensive global summary of the status of the resistance or susceptibility to Bt crops of 24 pest species in 12 countries. Another evaluates the inheritance and fitness costs of resistance of Diabrotica virgifera virgiferato Gpp34/Tpp35Ab (formerly called Cry34/35Ab). Two papers describe and demonstrate advances in techniques for monitoring field-evolved resistance. One uses a modified F2screen for resistance to Cry1Ac and Cry2Ab in Helicoverpa zeain the United States. The other uses genomics to analyze nonrecessive resistance to Cry1Ac in Helicoverpa armigerain China. Two papers provide multi-year monitoring data for resistance to Bt corn in Spain and Canada, respectively. The monitoring data from Spain evaluate responses to Cry1Ab of the corn borers Sesamia nonagrioidesand Ostrinia nubilalis, whereas the data from Canada track responses of O. nubilalisto Cry1Ab, Cry1Fa, Cry1A.105, and Cry2Ab. We hope the new methods, results, and conclusions reported here will spur additional research and help to enhance the sustainability of current and future transgenic insecticidal crops.

Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis(Bt) have provided control of some key pests since 1996. However, the evolution of resistance by pests reduces the benefits of Bt crops. Resistance to Bt crops that is not recessively inherited is especially challenging to manage. Here we analyzed nonrecessive resistance to Bt toxin Cry1Ac in eight field populations of Helicoverpa armigerasampled in 2018 from northern China, where this global pest has been exposed to Cry1Ac in Bt cotton since 1997. Bioassays revealed 7.5% of field-derived larvae were resistant to Cry1Ac of which 87% had at least one allele conferring nonrecessive resistance. To analyze this nonrecessive resistance, we developed and applied a variant of a genomic mapping approach called quantitative trait locus (QTL)-seq. This analysis identified a region on chromosome 10 associated with nonrecessive resistance to Cry1Ac in all 21 backcross families derived from field-collected moths. Individual sequencing revealed that all 21 field-collected resistant grandparents of the backcross families had a previously identified dominant point mutation in the tetraspanin gene HaTSPAN1that occurs in the region of chromosome 10 identified by QTL-seq. QTL-seq also revealed a region on chromosome 26 associated with nonrecessive resistance in at most 14% of the backcross families. Overall, the results imply the point mutation in HaTSPAN1is the primary genetic basis of nonrecessive resistance to Cry1Ac in field populations of H. armigerafrom northern China. Moreover, because nonrecessive resistance is predominant, tracking the frequency of this point mutation could facilitate resistance monitoring in the region.

Insecticidal proteins from the bacterium Bacillus thuringiensis(Bt) are used globally as bioinsecticides and in genetically engineered Bt crops to manage key insect pests. Transgenic Bt crops have been cumulatively planted on more than 1.5 billion hectares for more than 27 years, providing enhanced pest suppression, improved yields, increased farmer profits, and reduced environmental and health risks associated with the decreased use of conventional chemical insecticides. These benefits are reduced or lost when pests evolve resistance to Bt toxins in the field. Understanding the molecular genetic basis of resistance can be useful for monitoring, managing, and countering pest resistance to Bt crops. To date, 26 cases of field-evolved practical resistance and 18 cases of early warning of resistance to Bt crops have been reported, but the molecular genetic basis is known for only 9 of the 44 resistance cases to Bt crops. Here, we provide a comprehensive update on the molecular genetic mechanisms for these nine cases of field-evolved resistance to Bt crops and the numerous cases of laboratory-selected resistance to Bt toxins. We highlight lab-selected resistance involving regulation of Bt receptor genes and how recent research shows that regulatory pathways can be coopted to cause resistance. We further review recent technological advances in genomics and reverse genetics that have improved our ability to monitor and understand of the molecular genetic basis of pest resistance. The findings outlined here describe not only the complex genetic nature of Bt resistance, but also highlights new areas of exploration into the fundamental evolutionary basis of resistance mechanisms, which are important for sustaining the efficacy of currently available and future transgenic Bt crops.

• NiCoCrFeMoW HEAs with high density and sound velocity were developed. • Excellent quasi-static tensile and dynamic compression properties were achieved. • The dynamic flow behavior was successfully described by modified Johnson-Cook model. • Microbanding and twinning make major contribution on dynamic strengthening. High density alloys with enhanced deformability and strength are urgently required in energy, military and nuclear industries, etc. In this work, we present a new kind of NiCoFeCrMoW high entropy alloys (HEAs) which possess higher densities and sound velocities than copper. We systematically investigate the phase structure, quasi-static tensile, dynamic compression and related deformation mechanism of these HEAs. It is shown that single FCC or FCC + μ dual phases were formed in the HEAs depending on Mo and W content and annealing temperature. Excellent quasi-static tensile and dynamic compression properties have been achieved for these HEAs, e. g. Ni 30 Co 30 Fe 21 Cr 10 W 9 HEA annealed at 1573 K exhibited a yield and ultimate tensile strength and elongation of ∼364 MPa, ∼866 MPa and ∼32%, respectively, in quasi-static test; a yield strength of ∼710 MPa and no fracture under the dynamic strain rate of 4100 s−1. Superior strain rate sensitivity (SRS) of yield strength than that of previously reported FCC HEAs have been evidenced. The dynamic stress-strain constitutive relation can be described by the modified Johnson-Cook model. As for the dynamic deformation mechanism, it is envisaged that the regulation of stacking fault energy and Peierls barrier in current HEAs resulted in occurrences of abundant nanoscale deformation twins and microbands during high strain rate compression. The synergistic microbanding and twinning effectively contributes to the enhanced dynamic deformability and strengthening effect. Besides, the interactions of dislocations with precipitates, stacking faults (SFs) with twins, and between SFs also contribute to extraordinary work-hardening capacity. [Display omitted] [ABSTRACT FROM AUTHOR]

China consumes a large amount of fossil fuels to support its economic development, making it the world’s largest carbon emitter. To provide a solid basis for relevant policies and measures for energy conservation and emissions reduction, the evolution patterns of China’s energy use in trade were detailed analyzed in this article. The results showed that the ratio of net embodied energy flows to total energy consumption declined during the investigated period. The highly developed areas (such as Jiangsu, Zhejiang and Guangdong) imported embodied energy, while the least developed provinces (e.g., Guizhou and Yunnan) and areas with heavy industries (Hebei, Inner Mongolia and Shanxi) exported embodied energy. In terms of decomposition results, energy coefficients and per capita demand played dominant roles in determining energy consumption changes. Only the changes in the production trade structure represented obvious and continued negative spillover effects on energy decreases. The highly and least developed regions showed a reverse changing process in determining embodied energy flows, which was mainly due to structural factor changes. Moreover, per capita demand continued to boost the net embodied energy outflows of the provinces, with the economic structure relying highly on heavy industries. Finally, we proposed some effective policy suggestions by considering regional heterogeneity. The novelty of this paper is integrating the multi-regional input–output analysis and additive structural decomposition analysis to investigate the trajectory and drivers of China’s energy consumption footprint, respectively. Furthermore, driving factors behind embodied energy transfers were also analyzed.

ABSTRACTAlthough government-led housing affordability policy is an important issue worldwide, there has been little research on how local governments’ commitment to such policy affects people’s subjective well-being or happiness. By combining the analysis of textual information from provincial governments’ annual working reports and microdata from four waves of the China Household Finance Survey (CHFS), this article empirically explores the relationship between political discourses of provincial governments’ committment to housing affordability policies (HAPC) and residents’ self-reported happiness. Our results suggest that Chinese urban residents’ happiness is higher when the local government promises greater dedication to housing affordability improvement; however, this phenomenon existed only in the early 2010s, and the relationship between HAPC and residents’ happiness was insignificant in the mid-2010s, and even became negative in the late 2010s. In addition, we also find that the the association between HAPC and residents’ happiness differs among population groups. We conclude the article with discussions of the implications of the findings for housing policymaking and urban governance.

Entropy-stabilized multi-component alloys have been considered to be prospective structural materials attributing to their impressive mechanical and functional properties. The local chemical complexions, microstates and configurational transformations are essential to reveal the structure–property relationship, thus, to promote the development of advanced multi-component alloys. In the present work, effects of local lattice distortion (LLD) and microstates of various configurations on the equilibrium volume (V0), total energy, Fermi energy, magnetic moment (μMag) and electron work function (Φ) and bonding structures of the Fe–Mn–Al medium entropy alloy (MEA) have been investigated comprehensively by first-principles calculations. It is found that the Φand μMagof those MEA are proportional to the V0, which is dominated by lattice distortion. In terms of bonding charge density, both the strengthened clusters or the so-called short-range order structures and the weakly bonded spots or weak spots are characterized. While the presence of weakly bonded Al atoms implies a large LLD/mismatch, the Fe–Mn bonding pairs result in the formation of strengthened clusters, which dominate the local microstates and the configurational transitions. The variations of μMagare associated with the enhancement of the nearest neighbor magnetic Fe and Mn atoms, attributing to the LLD caused by Al atoms, the local changes in the electronic structures. This work provides an atomic and electronic insight into the microstate-dominated solid-solution strengthening mechanism of Fe–Mn–Al MEA.

ABSTRACTPurposeThis study reports clinical opinions and preferences on the non-surgical management of intermittent exotropia (IXT) among practitioners in China.MethodsAn online survey was developed and distributed through professional bodies. The study was conducted from July 25thto August 3rd, 2019. A total of 300 ophthalmologists and 188 optometrists responded.ResultsOf 488 participants, 257 (53%) considered fusion defects as the main cause of IXT, and 299 (61%) took IXT as a progressive disorder. Two hundred and seventy-one (56%) participants considered orthoptic exercises as the most effective non-surgical intervention for IXT. Likewise, 245 (50%) participants reported that orthoptic exercises were their most frequent non-surgical option, followed by observation (178, 37%). There are discrepancies between ophthalmologists and optometrists. A greater proportion of ophthalmologists (201, 67%) shared the view that IXT worsens over time (98, 52%) (p= .001). Additionally, ophthalmologists (121, 40%) tended to prefer observation compared with optometrists (57, 30%) (p= .021).ConclusionsThis study shows that there is no general consensus on the non-surgical management of IXT in China. Given the lack of robust evidence, the findings from this study highlight the need for future randomized clinical trials to validate the effectiveness of non-surgical interventions, orthoptic exercises in particular, and to establish treatment guidelines accordingly.

Zielsetzung: Untersuchung, ob klinische Variablen der postoperativen Binokularfunktion die langfristige Stabilität der postoperativen Augenstellung nach Korrektur einer intermittierenden Exotropie bei Kindern vorhersagen können. Methode: Es erfolgte eine retrospektive Studie zu 39 Kindern (medianes Alter: 7 Jahre), die wegen einer intermittierenden Exotropie operativ behandelt worden waren und bei denen keine Überkorrektur erfolgt war (weniger als 10 Prismen-Dioptrien (PDPT) Exodeviation 1 Monat nach der Operation). Präoperativ sowie 1 Monat und 6 Monate nach der Operation und bei der letzten Nachuntersuchung (≥24 Monate) des Patienten wurden die Schielwinkel und Variablen der Binokularfunktion bestimmt. Wir untersuchten die Beziehung zwischen postoperativer Drift (Änderung der Augenstellung) und Variablen der Binokularfunktion (sensorische Funktion, konvergente Fusionsbreite und Stereosehschärfe). Ergebnisse: Die Erfolgsrate der Operation (Esophorie/-tropie ≤5 PDPT bis Exophorie/-tropie ≤10 PDPT) hatte 6 Monate nach der Operation auf 76,9% und zum Zeitpunkt der letzten Nachuntersuchungen der Patienten (im Mittel nach 37 Monaten) auf 53,8% abgenommen. Die mittlere Exodrift betrug zwischen 1 Monat nach der Operation und der letzten Nachuntersuchung bei Fernfixation 7,7 ± 9,2 PDPT (p< 0,001). Die Stereosehschärfe in der Ferne, die zentrale Fusion und die konvergente Fusionsbreite verbesserten sich nach der Operation signifikant (p< 0,05). Allerdings wurde keine signifikante Korrelation zwischen den Binokularfunktionen zu Beginn jeder Nachbeobachtungsphase und der postoperativen Drift beobachtet (alle p> 0,13). Schlussfolgerung: Unsere Beobachtungen weisen darauf hin, dass die klinischen Variablen sensorische Fusion, konvergente Fusionsbreite und Stereosehschärfe bei erfolgreich operierten Patienten, die 1 Monat nach der Operation keine Überkorrektur zeigen, nicht als robuste Prädiktoren für die langfristige Stabilität der postoperativen, korrigierten Augenstellung geeignet sind.

ABSTRACTLong-term collective saving schemes are widely adopted in many emerging economies to support residents’ housing consumption. This article evaluates the effect of the Housing Provident Fund (HPF), one of the most prominent housing policies in China, on income redistribution beyond its housing support role. Based on micro survey data, our results suggest that the current HPF policy design widens the income gap between HPF participants and nonparticipants and aggravates income inequality across the whole population; further simulation results suggest that expanding HPF coverage has an alleviating effect. However, in the event of housing purchases through HPF loans, lower income participants can leverage more benefits, and the floor-and-ceiling policy design decreases the marginal benefits for higher income participants, resulting in mitigated income inequality among HPF participants. One notable risk of the HPF’s widening of the income gap among participants is the unavailability of HPF loans for low-income participants. Our findings indicate that optimizing the HPF system might be a better option than its abolishment, from the perspective of its income redistribution function. We also provide some valuable recommendations for gradual future reform of the HPF.

Transgenic crops producing insecticidal proteins from the bacterium Bacillus thuringiensis(Bt) have proven to be highly effective in managing some key pests. However, the evolution of resistance by the target pests threatens the sustainability of Bt crops. The L31S mutation in a tetraspanin encoded by HarmTspC5(previously known as HaTSPAN1) has been shown to confer dominant resistance to the Bt protein Cry1Ac in Helicoverpa armigera, a globally damaging lepidopteran pest. However, the broader implications of the L31S mutation in the tetraspanins of other lepidopteran species remain unclear. The evolutionary analyses in this study indicate that TspC5shave evolved in a species-specific manner among the lepidopteran insects. To investigate the role of TspC5sin conferring dominant resistance to Cry1Ac, we used the piggyBac-based transformation system to generate four transgenic H. armigerastrains that express exogenous TspC5variants from three phylogenetically close species (Helicoverpa zea, Helicoverpa assultaand Heliothis virescens) and one phylogenetically distant species (Plutella xylostella). In comparison with the background SCD strain of H. armigera, the transgenic strains expressing HzeaTspC5-L31S, HassTspC5-L31S, or HvirTspC5-L31S exhibited significant resistance to Cry1Ac (10.0-, 21.4-, and 81.1-fold, respectively), whereas the strain expressing PxylTspC5-L27S remained susceptible. Furthermore, the Cry1Ac resistant phenotypes followed an autosomal dominant inheritance pattern and were closely linked to the introduced mutant TspC5s. These findings reveal the conserved role of TspC5sfrom Helicoverpaand Heliothisspecies in mediating the dominant resistance to Cry1Ac, and they provide crucial insights for assessing resistance risks related to mutant tetraspanins and devising adaptive resistance management strategies for these major lepidopteran pests.

Fiber-based conductive films show great potential for use in electromagnetic interference shielding (EMI). However, it remains a challenge to meet the multifunctional requirements of ultrathin materials, such as simultaneous infrared stealth and outdoor stability. Here, this work prepared multilayer composite membranes composed of cellulose nanofiber layer (CNF), CNF/carbon nanotube@polypyrrole layer, and CNF/silver nanowire (AgNWs) layer in different sequences by a simple step-by-step vacuum filtration strategy and named them F, P, and A, respectively. Compared with the uniformly mixed film, the three-layer films have excellent shielding effectiveness (SE), attributed to the double gradient conductive network structure and loss of interfacial polarization. The P–F–A film, in particular, has a unique blank sandwich layer that makes the reflection and scattering paths of electromagnetic waves longer. As a result, the EMI SE of the P–F–A film is 69.8 dB, which is higher than those of F–P–A (64.06 dB) and F–A–P (63.8 dB). In addition, this work constructed a superhydrophobic surface by using 1H,1H,2H,2H-perfluorodecanethiol (PFDT) as the composite membranes. Because of the extremely low infrared emissivity of AgNWs, F–P–A and P–F–A films have excellent infrared stealth capabilities, and their performances are not affected by bending and abrasion, which can meet the requirements of multifunctions and adapt to complex environments. Overall, the composite films designed in this study have broad application prospects in flexible electronics wearable products, radar stealth, aerospace, and other fields.

Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1–3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6–10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength–ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank–Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.

The global spread of carbapenem-resistant Enterobacterales is a leading public-health threat. Lack of effective treatment has resulted in use of colistin as a last-resort therapeutic option for multidrug-resistant (MDR) bacterial infections. Here we report the complete genome sequence of a MDR Escherichia colistrain carrying a plasmid-mediated colistin resistance gene mcr-1recovered from a Chinese paediatric patient.

Here we report a complete genome sequence of a multidrug-resistant (MDR) SalmonellaRissen which carrying blaCTX-M-55and Tn6777isolated from a Chinese paediatric patient.

For near-β high-strength titanium alloys, rheological softening is the key step during thermal deformation to determine the microstructure and mechanical properties. Nevertheless, the intrinsic softening mechanism during the rheological stage is still an open question due to the special complexity of the process. In this study, the deformation process of near-β titanium alloy TC18 (Ti–5Al–5Mo–5V–1Cr–1Fe, wt.%) in a dual-phase region at a high strain rate was investigated. The micromechanical behavior of TC18 alloy during thermal deformation at 785 °C and 0.1/s was revealed by using in-situ high-energy X-ray diffraction (HEXRD). The stress partitioning and microstructure evolution mechanism for this alloy were discussed in detail. It has been confirmed that the main softening mechanisms of TC18 alloy during thermal deformation are dynamic recovery (DR) and continuous dynamic recrystallization (cDRX). The stress partitioning between constituent phases featured by higher stress in the α phase than in the β phase induces an inhomogeneous strain field near α phase lamellae to promote the dislocation pile-up in subgrains. The cDRX process of β grains is composed of dislocation slipping, DR and subgrains formation, and transformation of recrystallized grains with high-angle grain boundaries (HAGB). Schmid factor and micro stress have a remarkable effect on dynamic recrystallization (DRX) behavior. The soft <200>β//LD oriented grains are more likely to undergo cDRX than the hard <111>β//LD oriented grains. This work may have implications for understanding the deformation mechanism and provide a fundamental basis for selecting appropriate processing technology for near-β titanium alloys.

The purpose of this study was to investigate the effect of blue light phototherapy on the expression of circadian genes in peripheral blood mononuclear cells (PBMC) and plasma melatonin levels in neonates. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was used to determine the expression of Bmal1and Cry1in PBMC, and an enzyme-linked immunosorbent assay was used to determine plasma melatonin levels in 32 breast-milk jaundiced neonates before and after phototherapy, compared with 29 control neonates. The results showed that the expression of Bmal1was decreased and Cry1increased significantly after phototherapy. Plasma melatonin levels were decreased after phototherapy. There was no statistical difference in Bmal1and Cry1gene expression and plasma melatonin levels in the control group. In conclusion, phototherapy does affect the expression of the circadian genes Bmal1and Cry1in PBMC and plasma melatonin concentration in jaundiced neonates. Our results suggest that phototherapy should be timed according to circadian rhythms when treating jaundiced neonates.

The purpose of this study was to investigate the effect of blue light phototherapy on the expression of circadian genes in peripheral blood mononuclear cells (PBMC) and plasma melatonin levels in neonates. Real-time reverse-transcriptase polymerase chain reaction (RT-PCR) was used to determine the expression of Bmal1 and Cry1 in PBMC, and an enzyme-linked immunosorbent assay was used to determine plasma melatonin levels in 32 breast-milk jaundiced neonates before and after phototherapy, compared with 29 control neonates. The results showed that the expression of Bmal1 was decreased and Cry1 increased significantly after phototherapy. Plasma melatonin levels were decreased after phototherapy. There was no statistical difference in Bmal1 and Cry1 gene expression and plasma melatonin levels in the control group. In conclusion, phototherapy does affect the expression of the circadian genes Bmal1 and Cry1 in PBMC and plasma melatonin concentration in jaundiced neonates. Our results suggest that phototherapy should be timed according to circadian rhythms when treating jaundiced neonates.

In this study, blood culture and PCR-microarray analysis were used to examine 172 cases of suspected septicemia. Primers and oligonucleotide probes, based on the sequences of bacterial 16SrRNA gene, were arrayed by imprinting on microarray slides. Blood specimens collected from 172 cases of suspected septicemia were cultured and then tested separately by PCR for the bacterial 16S rRNA. Of the 172 clinical cases, 17 cases tested positive by PCR. The number of positives identified by PCR (9.88%) was significantly higher than the number of positives identified by the blood culture (4.65%). When blood culture was used as control, the sensitivity of PCR was 100%, the specificity was 97.85%, and the index of accurate diagnosis was 0.979. When the 17 PCR positive specimens were further analyzed by hybridization against the microarrays, five were found to be probe positive for E. coli, four were positive for S. epidermidis, four were positive for CoNS, and two were positive for Bacillusand Propionibacterium, respectively. In the eight specimens showing positive results by both PCR and blood culture, the species determined by microarray analysis corresponded with the result obtained from blood culture. Detection of the bacterial 16SrRNA genes in clinical specimens by PCR and microarray analysis can be used to accurately diagnose neonatal sepsis. This method has a higher sensitivity and specificity than blood culture and can provide a rapid way for the etiological diagnosis of neonatal septicemia.

In this study, blood culture and PCR-microarray analysis were used to examine 172 cases of suspected septicemia. Primers and oligonucleotide probes, based on the sequences of bacterial 16SrRNA gene, were arrayed by imprinting on microarray slides. Blood specimens collected from 172 cases of suspected septicemia were cultured and then tested separately by PCR for the bacterial 16S rRNA. Of the 172 clinical cases, 17 cases tested positive by PCR. The number of positives identified by PCR (9.88%) was significantly higher than the number of positives identified by the blood culture (4.65%). When blood culture was used as control, the sensitivity of PCR was 100%, the specificity was 97.85%, and the index of accurate diagnosis was 0.979. When the 17 PCR positive specimens were further analyzed by hybridization against the microarrays, five were found to be probe positive for E. coli, four were positive for S. epidermidis, four were positive for CoNS, and two were positive for Bacillus and Propionibacterium, respectively. In the eight specimens showing positive results by both PCR and blood culture, the species determined by microarray analysis corresponded with the result obtained from blood culture. Detection of the bacterial 16SrRNA genes in clinical specimens by PCR and microarray analysis can be used to accurately diagnose neonatal sepsis. This method has a higher sensitivity and specificity than blood culture and can provide a rapid way for the etiological diagnosis of neonatal septicemia.

Change history: In this Letter, owing to a production error, all the data points (except the two points for O-2 and N-2, respectively) were missing in Fig. 1b. The figure has been corrected online.

A field-collected strain (HF) of Plutella xylostella (L.) showed 420-fold resistance to fipronil compared with a susceptible laboratory strain (Roth). The HF-R strain, derived from the HF strain by 25 generations of successive selection with fipronil in the laboratory, developed 2,200-fold resistance to fipronil relative to the Roth strain. The F1 progeny of the reciprocal crosses between HF-R and Roth showed 640-fold (R♀ × S♂) and 1,380-fold (R♂ × S♀) resistance to fipronil, indicating resistance is inherited as an incompletely dominant trait. Analysis of progeny from a backcross (F1♂ × S♀) suggests that resistance is controlled by one major locus. The LC50 of the R♂ × S♀ cross F1 progeny is slightly but significantly higher than that of the R♀ × S♂ cross F1 progeny, suggesting a minor resistance gene on the Z chromosome. Sequence analysis of PxGABARα1 (an Rdl-homologous GABA receptor gene of P. xylostella) from the HF-R strain identified two mutations A282S and A282G (corresponding to the A302S mutation of the Drosophila melanogaster Rdl gene), which have been previously implicated in fipronil resistance in several insect species including P. xylostella. PxGABARα1 was previously mapped to the Z chromosome of P. xylostella. In conclusion, fipronil resistance in the HF-R strain of P. xylostella was incompletely dominant, and controlled by a major autosomal locus and a sex-linked minor gene (PxGABARα1) on the Z chromosome.

Beet armyworm, Spodoptera exigua (Hu¨bner), is a worldwide pest of many crops. Chemical insecticides are heavily used for its control in China, and serious resistance has been evolved in the field to a variety of insecticides including emamectin benzoate. Through repeated backcrossing to a susceptible strain (WH-S) and selection with emamectin benzoate, the trait conferring resistance to emamectin benzoate in a field-collected population of S. exigua (moderately resistant to emamectin benzoate and strongly resistant to pyrethroids and indoxacarb) was introgressed into WH-S to generate a near-isogenic resistant strain (WH-EB). Compared with WH-S, the WH-EB strain developed a 1,110-fold resistance to emamectin benzoate and a high level of cross-resistance to abamectin (202-fold), with low levels of cross-resistance to cypermethrin (10-fold) and chlorfluazuron (7-fold), but no cross-resistance to representatives of another six different classes of insecticides (chlorantraniliprole, chlorfenapyr, indoxacarb, spinosad, tebufenozide, and chlorpyrifos). Resistance to emamectin benzoate in WH-EB was autosomal, incompletely dominant, and polygenic. Limited cross-resistance in WH-EB indicates that emamectin benzoate can be rotated with other classes of insecticides to which it does not show cross-resistance to delay the evolution of resistance in S. exigua. The incompletely dominant nature of resistance in S. exigua may explain the rapid evolution of resistance to emamectin benzoate in the field, and careful deployment of this chemical within a resistance management program should be considered.

Beet armyworm, Spodoptera exigua (Hübner), is a serious pest of vegetables in China, and its control is heavily dependent on chemical insecticides. The current resistance status of nine insecticides was investigated in 16 field populations collected from seven provinces of China during 2009–2012. Compared with the susceptible strain WH-S, some field populations evolved various levels of resistance to eight of the nine insecticides tested: emamectin benzoate (4- to 348-fold), indoxacarb (2- to 41-fold), spinosad (5- to 38-fold), chlorantraniliprole (2- to 44-fold), tebufenozide (2- to 87-fold), chlorfluazuron (3- to 31-fold), cypermethrin (79- to 1240-fold), and chlorpyrifos (8- to 3,080-fold), but no significant resistance was detected to chlorfenapyr (0.4- to 7-fold). This indicates that chlorfenapyr has no cross-resistance with these other currently used insecticides. Four consecutive years' resistance screening at two places shows that resistance patterns were different between populations from Luhe (Jiangsu Province) and Fengxian (Shanghai), which are ≈300 km apart. Resistance levels to chlorpyrifos were much higher in populations from Luhe (877- to 3,080-fold) than from Fengxian (8- to 110-fold). Fengxian populations developed moderate levels of resistance to tebufenozide (13- to 87-fold), but no resistance in Luhe populations (2- to 6-fold). However, Luhe populations developed moderate levels of resistance to chlorfluazuron (21- to 31-fold), but there was no resistance in Fengxian populations (3- to 5-fold). It is suggested that local insecticide selection determined resistance patterns although S. exigua has long-distance migratory potential. Adaptive resistance management tactics (such as rotations) should be designed and implemented based on the resistance patterns of S. exigua for each geographic area.

Diamondback moth, Plutella xylostella (L.) is a serious insect pest of vegetables worldwide, and has evolved resistance to various kinds of insecticides. Studies were conducted to determine the baseline toxicity of metaflumizone and the possibility of cross-resistance between metaflumizone and indoxacarb, two sodium channel blocking insecticides (SCBIs), in field populations of P. xylostella from China. The variation in susceptibility to metaflumizone among 29 field populations of P. xylostella collected from 14 geographical locations in China was less than five-fold, with 50% lethal concentrations (LC50s) varying from 1.34 to 6.55 mg/liter. Limited variations in LC50s (less than five-fold, ranging from 1.76 to 8.16 mg/liter) were also observed in the four laboratory-selected strains with high levels of resistance to abamectin, spinosad, fipronil, or Bt toxin Cry1Ac. The toxicity of metaflumizone and indoxacarb was compared among 23 out of the 29 field populations. When compared with the susceptible Roth strain, the JN-09B population showed the highest level of resistance to indoxacarb (110-fold), but two-fold tolerance to metaflumizone. The other 22 populations (with 5- to 58-fold of resistance to indoxacarb) had 1- to three-fold tolerance to metaflumizone. Metaflumizone could provide an effective alternative insecticide for diamondback moth management. Although the field populations of P. xylostella tested with various levels of resistance to indoxacarb did not have cross-resistance to metaflumizone, metaflumizone should be rotated with other chemicals of different modes of action instead of indoxacarb.

Insecticide resistance was an important factor responsible for outbreaks of Helicoverpa armigera (Hübner) in China in the early 1990s. Bt cotton has been adopted in China since 1997, and has resulted in a reduction of insecticide use for H. armigera control. After 15 yr of Bt cotton planting, in 2011 we surveyed resistance to fenvalerate, phoxim, and emamectin benzoate in 16 field populations of H. armigera collected from major cotton production areas of China. Fourteen populations from northern China showed very strong resistance to fenvalerate (from 43- to 830-fold) and low levels of resistance to phoxim (3.0- to 8.9-fold) when compared with the susceptible SCD strain of H. armigera, whereas two populations from northwestern China showed low levels of resistance to fenvalerate (3.0- and 10-fold) and no resistance to phoxim (0.7- and 0.9-fold). Synergist bioassays demonstrated that oxidase-based detoxification was involved in fenvalerate resistance and esterase-based detoxification in phoxim resistance in the resistant field populations. In comparison with the resistance in field populations before Bt cotton adoption, we observed a maintenance of high levels of fenvalerate resistance, but a reversion of phoxim resistance from high levels to low levels in the field populations of H. armigera from northern China. All 16 field populations from both northern China and northwestern China were susceptible to emamectin benzoate (with about two-fold variations in LD50s among populations), but the SCD strain has an inherent tolerance of 11-fold compared with the most susceptible field population (Xiajin-1). Emamectin benzoate is not cross resistant to fenvalerate and may provide an alternative option for H. armigera control in China, if the efficacy of Bt cotton is compromised by Bt resistance in the field.

Chlorantraniliprole is the first commercial insecticide from a new class of chemistry, the anthranilic diamides. Chlorantraniliprole provides an effective alternative insecticide for control of Plutella xylostella (L.) populations resistant to other insecticides. Baseline susceptibility to chlorantraniliprole for P. xylostella was surveyed previously from 16 geographical populations sampled from China during 2008–2009, and the median lethal concentrations (LC50s) varied among populations from 1.8- to 8.9-fold higher than the LC50 of a susceptible strain (Roth). In the present work, 20 field populations of P. xylostella sampled in 2010–2011 from China were tested with laboratory bioassays to determine if resistance to chlorantraniliprole had evolved in the field. The LC50s of the 14 populations from northern China ranged from 1.7- to 5.4-fold compared with the LC50 of Roth, which indicates these populations remain reasonably susceptible to chlorantraniliprole. However, the LC50s of the six populations from southern China (Guangdong Province) were 2.6-, 12-, 18-, 81-, 140-, and 2,000-fold higher than the LC50 of Roth. The results showed that high levels of resistance to chlorantraniliprole had evolved in field populations from Guangdong Province of southern China. Intensive use and misuse of chlorantraniliprole may be responsible for the rapid evolution of high-level resistance in P. xylostella in this region. The implementation of resistance monitoring plans and resistance management strategies is urgently needed in China to preserve susceptibility to chlorantraniliprole in P. xylostella.

Diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), has evolved resistance to various kinds of insecticides in the field. Chlorantraniliprole, which is a new pesticide of the anthranilic diamide group, provides potent and broad-spectrum activity within the insect order Lepidoptera. This insecticide provides a new option for control of P. xylostella populations resistant to other chemicals. The susceptibility of 16 field populations and seven laboratory maintained strains of P. xylostella to chlorantraniliprole were determined through leaf dip bioassay. The susceptibility variation among 16 field populations was low (five-fold), with median lethal concentrations (LC50 values) varying from 0.221 to 1.104 mg/liter. However, wider ranges of variation in LC50 values (10-fold) were observed among seven laboratory strains. Low level tolerance (six- to 10-fold) was detected in two laboratory-selected strains and three field-collected populations when compared with the susceptible Roth strain. A discriminating concentration (15 mg/liter) was calibrated from pooled toxicological data of the 16 field populations, as an important first step in resistance management, for the routine monitoring of resistance in the future. When assessed at the established discriminating dose 15 mg/liter, seven laboratory strains and five field populations showed an average mortality of 99.75% (from 98 to100%). Synergism assays showed metabolic enzymes might be involved in chlorantraniliprole detoxification in the susceptible Roth strain, but not in the additional observed tolerance of strains selected for resistance with other insecticides.

Our previous studies showed that enhanced cytochrome P450-mediated detoxification is a major mechanism responsible for pyrethroid resistance in a laboratory-selected strain (YGF) of Helicoverpa armigera (Hübner). Two new cytochrome P450 genes, CYP9A12 and CYP9A14 (encoding 531 and 530 amino acid residues, respectively) were isolated from the fat body of the YGF strain of H. armigera. The mRNA expression levels of these two CYP9 P450 genes, together with CYP6B7 and CYP4G8 (previously reported to be overexpressed in pyrethroid-resistant strains), were assessed by real-time quantitative reverse transcription-polymerase chain reaction in the final instars of a field-derived YG strain (with seven-fold resistance to the pyrethroid fenvalerate) and the YGF strain (selected from the YG strain with fenvalerate in the laboratory, with 1,690-fold resistance to fenvalerate). The mRNA expression levels of CYP9A12, CYP9A14, and CYP6B7 in the fat body of the YGF strain increased to 433-, 59-, and 9.3-fold, respectively, compared with the YG strain, whereas no overexpression was revealed for CYP4G8. CYP9A12 and CYP9A14 had 19- and 4.3-fold overexpression in the midgut of the YGF strain compared with the YG strain, respectively, but CYP6B7 and CYP4G8 were not overexpressed. The current study provided evidence that constitutive overexpression of multiple cytochrome P450 genes (CYP9A12, CYP9A14, and CYP6B7) is associated with pyrethroid resistance in H. armigera.

The SZ-F strain of Plutella xylostella (L.) (Lepidoptera: Plutellidae) was derived from a field-collected strain (SZ) by 20 generations of continuous selection with fipronil. The selection resulted in 300-fold increase in resistance to fipronil, and 3.5- and 6.5-fold cross-resistance to dieldrin and endosulfan, respectively, in the SZ-F strain compared with the unselected SZ strain. Analysis of detoxification enzyme activities and bioassay with synergists indicated that metabolic mechanisms are not important to fipronil resistance of the SZ-F strain and that the fipronil resistance is most likely attributed to target site insensitivity. The genomic DNA fragments flanking the second membrane-spanning region of Rdl γ-aminobutyric acid (GABA) receptor gene from P. xylostella, PxRdl, were cloned and sequenced. A single allele of the PxRdl gene (encoding A302 or allele PxRdl-Ala) was found in both the Roth (susceptible) and SZ strains. In addition to the wild-type allele PxRdl-Ala, the resistant SZ-F strain carried a mutant PxRdl allele with the conserved amino acid replacement A302GCC→ S302TCC (allele PxRdl-Ser). The mutant PxRdl-Ser allele frequency in the SZ-F strain was 30%. After treatment of 20 mg/l fipronil on the SZ-F strain, the PxRdl-Ser allele frequency in the survivors increased to 57%. High frequency of the PxRdl-Ala allele remaining in the resistant SZ-F strain suggested that the A302S mutation in the PxRdl gene is partially associated with fipronil resistance and that other mutation(s) in the PxRdl gene or other Rdl-like subunit(s) may contribute to fipronil resistance.

Cytochrome P450 monooxygenases are a major metabolic mechanism responsible for pyrethroid resistance in Helicoverpa armigera (Hübner) from Asia. Cytochrome P450-mediated O-demethylation activity toward p-nitroanisole (PNOD) of individual fourth instars was determined in five strains of H. armigera by using a microplate reader. The four resistant strains of YS, HD, YGF, and YG59 had 6-, 71-, 2,540-, and 11,800-fold resistance, respectively, to fenvalerate in comparison with the susceptible BK77 strain. Their mean PNOD activity was 4-, 10-, 24-, and 60-fold, respectively, compared with the BK77 strain. A strong positive correlation (correlation coefficient r = 0.98) between PNOD activity and fenvalerate resistance was found. Of 48 larvae from each strain, only 4% larvae of the susceptible BK77 strain had detectable PNOD activity, whereas 25, 33, 79, and 96% of larvae from the resistant strains YS, HD, YGF, and YG59 exhibited PNOD activity, respectively. There was a clear discrimination of patterns of PNOD frequency distribution between H. armigera strains and their magnitudes of fenvalerate resistance. The PNOD activity can be used as a biochemical marker for monooxygenase-mediated pyrethroid resistance in field populations of H. armigera.

Cytochrome P450 monooxygenases are a major metabolic mechanism responsible for pyrethroid resistance in Helicoverpa armigera (Hübner) from Asia. Cytochrome P450-mediated O-demethylation activity toward p-nitroanisole (PNOD) of individual fourth instars was determined in five strains of H. armigera by using a microplate reader. The four resistant strains of YS, HD, YGF, and YG59 had 6-, 71-, 2,540-, and 11,800-fold resistance, respectively, to fenvalerate in comparison with the susceptible BK77 strain. Their mean PNOD activity was 4-, 10-, 24-, and 60-fold, respectively, compared with the BK77 strain. A strong positive correlation (correlation coefficient r = 0.98) between PNOD activity and fenvalerate resistance was found. Of 48 larvae from each strain, only 4% larvae of the susceptible BK77 strain had detectable PNOD activity, whereas 25, 33, 79, and 96% of larvae from the resistant strains YS, HD, YGF, and YG59 exhibited PNOD activity, respectively. There was a clear discrimination of patterns of PNOD frequency distribution between H. armigera strains and their magnitudes of fenvalerate resistance. The PNOD activity can be used as a biochemical marker for monooxygenase-mediated pyrethroid resistance in field populations of H. armigera.